ABL1

Summary

ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase, HGNC:76) is a protein-coding gene on chromosome 9q34.12, encoding Tyrosine-protein kinase ABL1 (P00519). Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. In precision oncology, BCR::ABL1 Fusion AND ABL1 T315I confers sensitivity to Ponatinib in B-lymphoblastic Leukemia/lymphoma (CIViC Level A); 287 further curated variant–drug associations are listed below.

This gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5’ end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons.

Source: NCBI Gene 25 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart defects and skeletal malformations syndrome (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 959 total — 13 pathogenic, 12 likely-pathogenic (top 3% of genes corpus-wide)
• Regional missense constraint (gnomAD): 2 of 7 regions constrained (≈11% of expected missense variation)
• GTEx eGene: eQTL in 22 tissues, sQTL in 6 (q < 0.05)
• Phenotypes (HPO): 62
• Drug target: yes — 18 curated mechanism-of-action drugs, 3 via a complex or family; 122 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 7 — Asciminib, Bosutinib, Dasatinib Anhydrous, +4 more
• Approved drugs acting on a complex or family including it: 1 — Ponatinib Hydrochloride (Bcr/Abl fusion protein)
• Precision-oncology evidence (CIViC): 288 curated variant–drug associations
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.19 (highly constrained)
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_005157
• Interaction hub: 3,972 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:76
Approved symbol	ABL1
Name	ABL proto-oncogene 1, non-receptor tyrosine kinase
Location	9q34.12
Locus type	gene with protein product
Status	Approved
Aliases	JTK7, c-ABL, p150
Ensembl gene	ENSG00000097007
Ensembl biotype	protein_coding
OMIM	189980
Entrez	25

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 3 nonsense_mediated_decay

MANE Select: ENST00000318560

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 5: 1

ENST00000318560, ENST00000372348, ENST00000393293, ENST00000929253, ENST00000929254, ENST00000929255, ENST00001067205, ENST00001067206, ENST00001067207

RefSeq mRNA: 2 — MANE Select: NM_005157 NM_005157, NM_007313

CCDS: CCDS35165, CCDS35166

Canonical transcript exons

ENST00000318560 — 11 exons

Exon	Start	End
ENSE00000984287	130854064	130854237
ENSE00001700841	130872860	130873037
ENSE00001715343	130880068	130880157
ENSE00001726283	130872129	130872213
ENSE00001741732	130878415	130878567
ENSE00001758713	130874868	130875052
ENSE00001781962	130880500	130880664
ENSE00001938256	130883969	130887675
ENSE00001955789	130835254	130835525
ENSE00002065214	130862763	130863035
ENSE00002690665	130854801	130855096

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 98.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.1575 / max 256.9575, expressed in 1818 samples.

Highest expression (Bgee): frontal pole, paraflocculus, middle frontal gyrus, muscle layer of sigmoid colon, mucosa of stomach.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ABL1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 22 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 28 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	3.4e-10	+0.23	9:130870100:A:G
Brain Cerebellar Hemisphere	eqtl	1.8e-08	+0.38	9:130869524:G:A
Testis	eqtl	2.7e-06	+0.25	9:130839379:T:G
Nerve Tibial	sqtl	3.4e-06	-0.36	9:130879895:T:G
Nerve Tibial	eqtl	1.7e-05	+0.21	9:130891158:G:A
Spleen	eqtl	2.4e-05	+0.25	9:130754682:G:GC
Stomach	eqtl	6.5e-05	-0.37	9:130852290:A:G
Adipose Subcutaneous	sqtl	6.8e-05	-0.41	9:130879895:T:G
Brain Cerebellum	eqtl	1.5e-04	+0.32	9:130827856:C:T
Adipose Subcutaneous	eqtl	3.5e-04	-0.35	9:130852290:A:G
Adrenal Gland	eqtl	3.6e-04	+0.39	9:129721909:T:A
Artery Tibial	sqtl	4.2e-04	+0.31	9:130888820:C:T
Cells EBV-transformed lymphocytes	eqtl	8.9e-04	-0.26	9:130805887:G:GT
Heart Left Ventricle	eqtl	1.5e-03	+0.18	9:130878645:A:G
Breast Mammary Tissue	sqtl	2.3e-03	-0.48	9:130879895:T:G
Pituitary	eqtl	3.0e-03	-0.26	9:130834685:G:C
Breast Mammary Tissue	eqtl	5.8e-03	+0.18	9:130878712:C:A
Thyroid	eqtl	7.3e-03	+0.14	9:130726254:T:TCCAC
Muscle Skeletal	eqtl	9.1e-03	-0.33	9:131106247:G:A
Skin Sun Exposed Lower leg	sqtl	1.1e-02	-0.35	9:130879895:T:G

FANTOM5 promoters

showing 10 of 11 alternative TSS:

Promoter ID	TPM avg	Samples expressed
99032	10.1391	1785
99038	9.7393	1654
99030	7.3310	1724
99034	1.1804	709
99031	0.8115	260
99035	0.5556	252
99037	0.4777	251
99039	0.3504	172
99033	0.3116	126
99036	0.2226	83

Top tissues by expression

showing 100 of 292 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	98.80	gold quality
paraflocculus	UBERON:0005351	98.69	gold quality
middle frontal gyrus	UBERON:0002702	98.68	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.54	gold quality
mucosa of stomach	UBERON:0001199	96.22	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.99	gold quality
lower esophagus	UBERON:0013473	95.96	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.87	gold quality
stromal cell of endometrium	CL:0002255	95.79	gold quality
left uterine tube	UBERON:0001303	95.62	gold quality
ventricular zone	UBERON:0003053	95.40	gold quality
body of uterus	UBERON:0009853	95.13	gold quality
ganglionic eminence	UBERON:0004023	95.11	gold quality
popliteal artery	UBERON:0002250	95.05	gold quality
tibial artery	UBERON:0007610	95.05	gold quality
endocervix	UBERON:0000458	94.94	gold quality
saphenous vein	UBERON:0007318	94.81	gold quality
sigmoid colon	UBERON:0001159	94.22	gold quality
aorta	UBERON:0000947	94.18	gold quality
right ovary	UBERON:0002118	94.00	gold quality
endometrium epithelium	UBERON:0004811	93.83	gold quality
left ovary	UBERON:0002119	93.82	gold quality
fundus of stomach	UBERON:0001160	93.58	gold quality
right coronary artery	UBERON:0001625	93.55	gold quality
transverse colon	UBERON:0001157	93.54	gold quality
smooth muscle tissue	UBERON:0001135	93.52	gold quality
right lobe of thyroid gland	UBERON:0001119	93.17	gold quality
gall bladder	UBERON:0002110	93.15	gold quality
descending thoracic aorta	UBERON:0002345	93.15	gold quality
pericardium	UBERON:0002407	93.14	gold quality
left lobe of thyroid gland	UBERON:0001120	93.12	gold quality
myometrium	UBERON:0001296	93.11	gold quality
ectocervix	UBERON:0012249	93.10	gold quality
colon	UBERON:0001155	93.08	gold quality
thoracic aorta	UBERON:0001515	93.04	gold quality
ascending aorta	UBERON:0001496	93.02	gold quality
urethra	UBERON:0000057	92.99	gold quality
secondary oocyte	CL:0000655	92.86	gold quality
omental fat pad	UBERON:0010414	92.83	gold quality
peritoneum	UBERON:0002358	92.81	gold quality
left coronary artery	UBERON:0001626	92.78	gold quality
coronary artery	UBERON:0001621	92.75	gold quality
thyroid gland	UBERON:0002046	92.64	gold quality
embryo	UBERON:0000922	92.63	gold quality
large intestine	UBERON:0000059	92.62	gold quality
ileal mucosa	UBERON:0000331	92.60	gold quality
urinary bladder	UBERON:0001255	92.59	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.50	gold quality
inferior olivary complex	UBERON:0002127	92.41	gold quality
cortical plate	UBERON:0005343	92.33	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.30	gold quality
synovial joint	UBERON:0002217	92.16	gold quality
intestine	UBERON:0000160	91.99	gold quality
body of stomach	UBERON:0001161	91.99	gold quality
inferior vagus X ganglion	UBERON:0005363	91.92	gold quality
esophagus	UBERON:0001043	91.80	gold quality
ovary	UBERON:0000992	91.72	gold quality
adrenal tissue	UBERON:0018303	91.62	gold quality
trachea	UBERON:0003126	91.51	gold quality
adenohypophysis	UBERON:0002196	91.41	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.40	gold quality
stomach	UBERON:0000945	91.39	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.26	gold quality
spinal cord	UBERON:0002240	91.17	gold quality
tibial nerve	UBERON:0001323	91.09	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	91.09	gold quality
adipose tissue	UBERON:0001013	91.07	gold quality
cardia of stomach	UBERON:0001162	91.05	gold quality
skin of leg	UBERON:0001511	90.91	gold quality
decidua	UBERON:0002450	90.90	gold quality
lower esophagus mucosa	UBERON:0035834	90.80	gold quality
mammary duct	UBERON:0001765	90.75	gold quality
layer of synovial tissue	UBERON:0007616	90.74	gold quality
oocyte	CL:0000023	90.65	gold quality
connective tissue	UBERON:0002384	90.58	gold quality
small intestine	UBERON:0002108	90.53	gold quality
right atrium auricular region	UBERON:0006631	90.48	gold quality
pituitary gland	UBERON:0000007	90.38	gold quality
colonic epithelium	UBERON:0000397	90.25	gold quality
vagina	UBERON:0000996	90.23	gold quality
nipple	UBERON:0002030	90.19	gold quality
minor salivary gland	UBERON:0001830	90.15	gold quality
uterus	UBERON:0000995	90.08	gold quality
cardiac atrium	UBERON:0002081	90.05	gold quality
upper lobe of left lung	UBERON:0008952	90.04	gold quality
prostate gland	UBERON:0002367	90.03	gold quality
upper lobe of lung	UBERON:0008948	90.00	gold quality
rectum	UBERON:0001052	89.99	gold quality
mucosa of transverse colon	UBERON:0004991	89.92	gold quality
skin of abdomen	UBERON:0001416	89.91	gold quality
female reproductive system	UBERON:0000474	89.87	gold quality
postcentral gyrus	UBERON:0002581	89.77	gold quality
lower lobe of lung	UBERON:0008949	89.70	gold quality
saliva-secreting gland	UBERON:0001044	89.65	gold quality
epithelium of mammary gland	UBERON:0003244	89.65	gold quality
apex of heart	UBERON:0002098	89.56	gold quality
caecum	UBERON:0001153	89.48	gold quality
left adrenal gland cortex	UBERON:0035825	89.37	gold quality
vena cava	UBERON:0004087	89.32	gold quality
zone of skin	UBERON:0000014	89.30	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Corpus callosum	tissue	73.7
Choroid plexus	tissue	68.3
Substantia nigra	tissue	45.7
Medulla oblongata	tissue	43.0
Vagina	tissue	40.9	medium
Superior colliculi	tissue	40.6
Nucleus accumbens	tissue	40.1
Locus coeruleus	tissue	40.0
Spinal cord	tissue	40.0
Hippocampus	tissue	40.0	low
Midbrain	tissue	39.7
Endometrium 1	tissue	37.4	medium
Thalamus	tissue	36.4
Periaqueductal gray	tissue	35.4
Smooth muscle	tissue	34.8	low
Pituitary gland	tissue	34.5
Urinary bladder	tissue	34.3	medium
Pons	tissue	34.1
Ventral forebrain	tissue	33.5
Putamen	tissue	33.4
Hypothalamus	tissue	32.9
Ovary	tissue	31.4	low
Adipose tissue	tissue	31.2	low
Gallbladder	tissue	30.0	medium
Seminal vesicle	tissue	28.3	medium
Cervix	tissue	28.0	medium
Esophagus	tissue	27.8	low
Septum	tissue	27.6
Hippocampal formation	tissue	27.2
Colon	tissue	25.5	medium
Fallopian tube	tissue	24.7	medium
Tongue	tissue	24.6
Postcentral gyrus	tissue	24.2
Salivary gland	tissue	23.3	medium
Parathyroid gland	tissue	22.5	low
Amygdala	tissue	22.0
Thyroid gland	tissue	21.8	medium
Placenta	tissue	21.7	high
Prostate	tissue	21.1	low
Appendix	tissue	21.0	low
Pancreas	tissue	20.5	low
Basal ganglia	tissue	20.3	low
Rectum	tissue	20.1	medium
Cerebral cortex	tissue	19.7	low
Retrosplenial cortex	tissue	19.7
Caudate putamen	tissue	18.9
Somatosensory cortex	tissue	18.7
Olfactory bulb	tissue	18.6
Motor cortex	tissue	18.4
Insular cortex	tissue	18.4
Small intestine	tissue	17.7	medium
Bone marrow	tissue	17.5	low
Occipital cortex	tissue	17.4
Prefrontal cortex	tissue	17.0
Skeletal muscle	tissue	16.8	medium
Duodenum	tissue	16.8	medium
Heart muscle	tissue	16.7	medium
Spleen	tissue	16.3	medium
Thymus	tissue	16.3
Lung	tissue	16.1	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (73.7), Temporal white matter (70.8), Area postrema (70.4), Nucleus raphe obscurus (69.8), Parieto-temporal junction (white matter) (69.5).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

10 targets:

Target	Regulation
BAX	Activation
BCL2	Repression
BCL6	Repression
CCND2	Activation
CDKN1A	Activation
CSF1	Activation
FOXO3	Activation
JUN	Activation
PIM1	Activation
TP53	Activation

Upstream regulators (CollecTRI, top): AP1, BCL6, CUX1, EGR1, ESR1, GFI1, HAND2, HHEX, HIF1A, HR, IRF8, JUN, KAT5, MYC, NFKB, PAX1, PAX5, RELA, RUNX1, SALL2, SATB1, SP1, SPI1, STAT1, STAT5A, TBX21, TCF3, TFAP2A, TP53, TXK, ZHX2

miRNA regulators (miRDB)

Targeting ABL1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 79 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4320	99.75	65.80	793

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.19, missense Z 4.29 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000318560 splits into 7 regions with different missense tolerance; 2 are missense-constrained (≈11% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
9:130,835,447–130,854,184	65 / 80.8	0.80	no
9:130,854,185–130,855,088	47 / 142.2	0.33	yes (p 1.4e-15)
9:130,855,089–130,862,805	22 / 23.0	0.96	no
9:130,862,806–130,873,019	92 / 212.3	0.43	no
9:130,873,020–130,874,894	0 / 18.1	0.00	yes (p 2.1e-05)
9:130,874,895–130,880,523	76 / 177.1	0.43	no
9:130,880,524–130,885,680	780 / 835.8	0.93	no

Literature-anchored findings (GeneRIF, showing 40)

• The abl protein was analyzed by real time quantitative PCR. (PMID:11708318)
• crystal structure of the Bcr-Abl oncoprotein oligomerization domain (PMID:11780146)
• regulates p73 through p38 MAP kinase pathway (PMID:11840343)
• These findings indicate that Rad9 is regulated by a c-Abl-dependent mechanism in the apoptotic response to genotoxic stress. (c-abl protein) (PMID:11971963)
• C terminus of BRCA1 is phosphorylated by c-Abl in vitro (PROTO-ONCOGENE C-ABL) (PMID:12024016)
• Several types of mutations of the Abl gene can be found in chronic myeloid leukemia patients resistant to STI571, and they can pre-exist to the onset of treatment. (PMID:12130516)
• This review focuses on how Bcr-Abl affects HSCs and how Bcr-Abl expression alters the properties of HSCs. (PMID:12138893)
• chronic myelogenous leukemia characterized by translocation between chromosomes 9 and 22 forming a BCR-ABL gene, a specific marker for this disease. (PMID:12144533)
• mutations of Tyr-253 in the nucleotide-binding (P) loop of the Abl kinase domain to Phe or His in patients with advanced CML and acquired STI-571 resistance (PMID:12149456)
• The data showed that c-abl expression is differently modified in lymphoid B cell lines. (PMID:12220663)
• Review. ABL protein tyrosine kinases regulate cell proliferation, survival, adhesion, migration, stress responses, and cytoskeletal dynamics. (PMID:12374288)
• determined the NMR solution structure of the ternary complex of the Abl SH3 domain with the Crk SH2 domain bound to a Crk pY221 phosphopeptide (PMID:12384576)
• point mutations in Abl that rendered Bcr-Abl imatinib mesylate-resistant, including a mutation that destabilized the inactive conformation of Abl suggesting that the inhibitor required inactivation of the kinase prior to binding. (PMID:12393636)
• expression of bcr/abl hybridized gene in chronic myeloid leukemia (CML), acute lymphatic leukemia (ALL) and polycythemia vera (PV), and its clinical significance (PMID:12408765)
• Chronic myelocytic leukemia with eosinophilia, t(9;12)(q34;p13), and ETV6-ABL gene rearrangement: case report and review of the literature. (PMID:12505259)
• An inherited, apparently balanced translocation involving chromosomes 3(q22), 22(q12), and 9(q34.1, resulting from meiotic recombination, leads to deletion in the ABL gene in a child with axial hypotonia and dysmorphism. ) (PMID:12525554)
• constitutively activated Bcr-Abl kinase pathways in primitive CML progenitors cooperate with growth factors producing a growth response and disrupt the normally required synergistic interactions between kit ligand and other cytokines to achieve activation (PMID:12556557)
• concluded that the IRS-1 protein is involved in the signalling pathway of the BCR-ABL tyrosine kinase (PMID:12560071)
• detection of kinase domain mutations was almost always associated with imatinib resistance, and patients with mutations in the P-loop had a particularly poor prognosis (PMID:12623848)
• In conclusion, effective and prompt IR-induced Rad51 focus formation is cell cycle-regulated and requires both ATM and c-Abl. (PMID:12650908)
• This gene is regulated by a myristoyl/phosphotyrosine switch. (PMID:12654250)
• mechanism by which caspases can recruit c-Abl to the nuclear compartment and to the mammalian apoptotic program (PMID:12665579)
• c-Abl-mediated phosphorylation of Mena is regulated by Abi-1 (PMID:12672821)
• BCR-ABL is inhibited by lyp tyrosine phosphatase (PMID:12764153)
• Dok-R and c-Abl interact in both a constitutive and inducible fashion and Dok-R influences the intracellular kinase and biological activity of c-Abl (PMID:12777393)
• c-Abl and Arg regulate catalase and that this signaling pathway is of importance to apoptosis in the oxidative stress response (PMID:12777400)
• BCR/ABL amplification may play a role as a novel mechanism in the progression to an aggressive blast transformation in some cases of Philadelphia chromosome-positive chronic myelocytic leukemia (PMID:12781448)
• c-Abl increases the cellular p73 abundance through posttranslational regulation. Kinase activity is essential for c-Abl to up-regulate p73. c-Abl contributes to either pro- or antiapoptotic process depending on the expression profile of p73 isoforms. (PMID:12810679)
• c-Abl tyrosine kinase selectively regulates p73 nuclear matrix association (PMID:12824179)
• Expression of BCR/ABL and BCL-2 in myeloid progenitors leads to myeloid leukemias. (PMID:12890867)
• ABL-kinase domain point mutation as a cause of imatinib resistance in CML patient who progress to myeloid blast crisis (PMID:12921956)
• differential utilization of the p53 and c-Abl/p73 pathways by different tumor cell line. (PMID:12928501)
• we have identified a direct binding between WRN and c-Abl in vitro via the N-terminal and central regions of WRN and the Src homology domain 3 of c-Abl. These findings suggest a novel signaling pathway (PMID:12944467)
• findings indicate that, in addition to stimulating catalase activity, c-Abl and Arg promote catalase degradation in the oxidative stress response (PMID:12950161)
• The deletion of the 5’abl region on der(9), present in approximately 9% of the CML, takes place at the same time as the formation of the Ph chromosome translocation and seems of worse prognosis (PMID:12952226)
• the equilibrium fraction of c-Abl in which the myristoylated N-terminal is unlatched is approximately 0.5% (PMID:14527680)
• ABL fuses with BCR to form a fusion protein. (PMID:14534537)
• down-regulation of Bcr-Abl mRNA might be one of the mechanisms implicated in the apicidin-mediated apoptosis in the K562 cells (PMID:14581377)
• Describe RT-PCR/capillary electrophoresis method for quantification of bcr-abl transcripts in leukemia. (PMID:14657955)
• Bcr-Abl-mediated transformation involves transcriptional activation of the PKCiota gene, which in turn is required for Bcr-Abl-mediated chemoresistance (PMID:14670960)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	abl1	ENSDARG00000035187
mus_musculus	Abl1	ENSMUSG00000026842
rattus_norvegicus	Abl1	ENSRNOG00000047356

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), JAK2 (ENSG00000096968), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), CSK (ENSG00000103653), TYK2 (ENSG00000105397), JAK3 (ENSG00000105639), FRK (ENSG00000111816), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), SYK (ENSG00000165025), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:87859) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 74 distinct phenotype terms.

Mouse phenotype (MP)	Records
postnatal lethality, incomplete penetrance	4
decreased pro-B cell number	3
rectal prolapse	2
abnormal spleen morphology	2
decreased thymocyte number	2
abnormal immune system cell morphology	2
decreased body size	2
abnormal B cell differentiation	2
increased susceptibility to infection	2
spleen atrophy	2
thymus atrophy	2
decreased pre-B cell number	2
decreased cranium height	2
decreased survivor rate	2
abnormal bone marrow cell physiology	2
neonatal lethality, incomplete penetrance	2
abnormal heart morphology	1
enlarged heart	1
heart hyperplasia	1
abnormal myocardial fiber morphology	1
decreased bone marrow cell number	1
abnormal digestive system morphology	1
abnormal hepatocyte morphology	1
enlarged spleen	1
spleen hypoplasia	1

+49 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Felis catus	A0M8S8	100.0%	Diamond
Gallus gallus	P00523	100.0%	Diamond
Bos taurus	A0JNB0	99.6%	Diamond
Sus scrofa	A1Y2K1	99.4%	Diamond
Papio anubis	A0M8R7	99.3%	Diamond
Macaca mulatta	P55245	99.3%	Diamond
Xenopus laevis	P87379	98.7%	Diamond
Calliphora vicina	P11681	98.6%	Diamond
Canis lupus familiaris	A0A8I3NFE2	95.9%	Diamond
Xenopus tropicalis	A0JM20	95.5%	Diamond
Avian leukosis virus	P00534	100.0%	Diamond
Avian erythroblastosis virus (strain ts167)	P11273	100.0%	Diamond
Avian sarcoma virus PR2257	P15054	100.0%	Diamond
Avian sarcoma virus S2	P14085	99.8%	Diamond
Avian sarcoma virus S1	P14084	99.6%	Diamond
Avian erythroblastosis virus (strain ES4)	P00535	99.5%	Diamond
Feline sarcoma virus (STRAIN HARDY-ZUCKERMAN 2)	P10447	99.3%	Diamond
Gardner-Arnstein feline sarcoma virus	P00542	99.1%	Diamond
Snyder-Theilen feline sarcoma virus	P00543	99.1%	Diamond
Rous sarcoma virus (strain Schmidt-Ruppin A)	P00524	99.0%	Diamond
Avian sarcoma virus RASV1441	P00525	99.0%	Diamond
Rous sarcoma virus - Prague C	P00526	99.0%	Diamond
Rous sarcoma virus (strain H-19)	P25020	99.0%	Diamond
Rous sarcoma virus (strain Schmidt-Ruppin E)	P63185	99.0%	Diamond
Y73 sarcoma virus	P00527	98.9%	Diamond
Abelson murine leukemia virus	P00521	98.7%	Diamond
Rous sarcoma virus (strain PA101T)	P31693	95.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
EXOSC2	protein-coding	23404
LAMC3	protein-coding	10319
QRFP	protein-coding	347148
FIBCD1	protein-coding	84929
FIBCD1-AS1	ncRNA	105376297
PRDM12	protein-coding	59335
MIR6856	ncRNA	102465515
FUBP3	protein-coding	8939

Protein

Protein identifiers

Tyrosine-protein kinase ABL1 — P00519 (reviewed: P00519)

Alternative names: Abelson murine leukemia viral oncogene homolog 1, Abelson tyrosine-protein kinase 1, Proto-oncogene c-Abl, p150

All UniProt accessions (2): P00519, R4GRW0

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at ‘Tyr-717’. ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on ‘Tyr-153’ and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 also acts as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1. Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity.

Subunit / interactions. Interacts with SORBS1 following insulin stimulation. Found in a trimolecular complex containing CDK5 and CABLES1. Interacts with CABLES1 and PSTPIP1. Interacts with ZDHHC16, ITGB1 and HCK. Interacts with STX17; probably phosphorylates STX17. Interacts with INPPL1/SHIP2. Interacts with the 14-3-3 proteins, YWHAB, YWHAE, YWHAG, YWHAH, SFN and YWHAZ; the interaction with 14-3-3 proteins requires phosphorylation on Thr-735 and, sequesters ABL1 into the cytoplasm. Interacts with ABI1, ABI2, BCR, CRK, FGR, FYN, HCK, LYN, PSMA7 RAD9A, RAD51, RAD52, TP73 and WASF3. A complex made of ABL1, CTTN and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement. Interacts (via SH3 domain) with CASP9; the interaction is direct and increases in the response of cells to genotoxic stress and ABL1/c-Abl activation. Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases. Interacts with TBX21. Interacts with NEDD9/HEF1; interaction is induced by CXCL12 promotion of ABL-mediated phosphorylation of NEDD9/HEF1.

Subcellular location. Cytoplasm. Cytoskeleton. Nucleus. Mitochondrion Nucleus membrane.

Tissue specificity. Widely expressed.

Post-translational modifications. Acetylated at Lys-711 by EP300 which promotes the cytoplasmic translocation. Phosphorylation at Tyr-70 by members of the SRC family of kinases disrupts SH3 domain-based autoinhibitory interactions and intermolecular associations, such as that with ABI1, and also enhances kinase activity. Phosphorylation at Tyr-226 and Tyr-393 correlate with increased activity. DNA damage-induced activation of ABL1 requires the function of ATM and Ser-446 phosphorylation. Phosphorylation at Ser-569 has been attributed to a CDC2-associated kinase and is coupled to cell division. Phosphorylation at Ser-618 and Ser-619 by PAK2 increases binding to CRK and reduces binding to ABI1. Phosphorylation on Thr-735 is required for binding 14-3-3 proteins for cytoplasmic translocation. Phosphorylated by PRKDC. Polyubiquitinated. Polyubiquitination of ABL1 leads to degradation.

Disease relevance. Leukemia, chronic myeloid (CML) [MIM:608232] A clonal myeloproliferative disorder of a pluripotent stem cell with a specific cytogenetic abnormality, the Philadelphia chromosome (Ph), involving myeloid, erythroid, megakaryocytic, B-lymphoid, and sometimes T-lymphoid cells, but not marrow fibroblasts. The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving ABL1 has been found in patients with chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with BCR. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). A chromosomal aberration involving ABL1 is found in a form of acute lymphoblastic leukemia. Translocation t(9;9)(q34;q34) with NUP214. Congenital heart defects and skeletal malformations syndrome (CHDSKM) [MIM:617602] An autosomal dominant disorder characterized by congenital heart disease with atrial and ventricular septal defects, variable skeletal abnormalities, and failure to thrive. Skeletal defects include pectus excavatum, scoliosis, and finger contractures. Some patient exhibit joint laxity. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the N-terminal cap, and contributions from an N-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation. Activated by RIN1 binding to the SH2 and SH3 domains. Also stimulated by cell death inducers and DNA-damage. Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, also inhibits the tyrosine kinase activity. Activated by 5-(1,3-diaryl-1H-pyrazol-4-yl)hydantoin, 5-[3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl]-2,4-imidazolidinedione (DPH). Inhibited by ABI1, whose activity is controlled by ABL1 itself through tyrosine phosphorylation. Also inhibited by imatinib mesylate (Gleevec) which is used for the treatment of chronic myeloid leukemia (CML), and by VX-680, an inhibitor that also acts on imatinib-resistant mutants.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. ABL subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P00519-1	IA	yes
P00519-2	IB

RefSeq proteins (2): NP_005148, NP_009297 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000980	SH2	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001452	SH3_domain	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR015015	F-actin-binding	Domain
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR035837	ABL_SH2	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR050198	Non-receptor_tyrosine_kinases	Family

Pfam: PF00017, PF00018, PF07714, PF08919

Enzyme classification (BRENDA)

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea)

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (171 total): strand 34, helix 34, modified residue 34, sequence conflict 17, sequence variant 12, compositionally biased region 11, turn 8, short sequence motif 5, region of interest 4, domain 3, binding site 3, chain 1, lipid moiety-binding region 1, active site 1, site 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

showing 30 of 85 structures by resolution:

PDB	Title	Method	Resolution (Å)
5OAZ	Crystal structure of the Abl-SH3 domain at pH 7.5	X-RAY DIFFRACTION	1.03
7PVS	Crystal structure of the Abl SH3 domain V73E-A74S-S75R-G76T-D77E-G92N-Y93N-N94T-H95E …	X-RAY DIFFRACTION	1.05
4J9C	Crystal structure of the Abl-SH3 domain H59Q-N96T mutant complexed with the designed …	X-RAY DIFFRACTION	1.05
4J9F	Crystal structure of the Abl-SH3 domain complexed with the high affinity peptide P0	X-RAY DIFFRACTION	1.09
7PW2	Crystal structure of the Abl SH3 domain V73E-A74S-S75R-G76T-D77E mutant	X-RAY DIFFRACTION	1.1
3EG3	Crystal structure of the N114A mutant of ABL-SH3 domain	X-RAY DIFFRACTION	1.4
4J9E	Crystal structure of the N114A mutant of the Abl-SH3 domain complexed with the high …	X-RAY DIFFRACTION	1.4
5DC4	CRYSTAL STRUCTURE OF MONOBODY AS25/ABL1 SH2 DOMAIN COMPLEX, CRYSTAL A	X-RAY DIFFRACTION	1.48
4J9D	Crystal structure of the N114A mutant of the Abl-SH3 domain complexed with the high …	X-RAY DIFFRACTION	1.5
5HU9	Crystal structure of ABL1 in complex with CHMFL-074	X-RAY DIFFRACTION	1.53
7PVQ	Crystal structure of the Abl SH3 domain V73E-A74S-S75R-G76T-D77E-G92N-Y93N-N94T-H95E …	X-RAY DIFFRACTION	1.55
5DC9	CRYSTAL STRUCTURE OF MONOBODY AS25/ABL1 SH2 DOMAIN COMPLEX, CRYSTAL B	X-RAY DIFFRACTION	1.56
4JJC	Crystal structure of the Abl-SH3 domain at pH5	X-RAY DIFFRACTION	1.6
4JJD	Crystal structure of the N114A Abl-SH3 domain mutant at pH4	X-RAY DIFFRACTION	1.6
5NP2	Abl1 SH3 pTyr89/134	X-RAY DIFFRACTION	1.6
1BBZ	CRYSTAL STRUCTURE OF THE ABL-SH3 DOMAIN COMPLEXED WITH A DESIGNED HIGH-AFFINITY PEPTIDE …	X-RAY DIFFRACTION	1.65
4JJB	Crystal structure of the Abl-SH3 domain at pH3	X-RAY DIFFRACTION	1.65
7PVR	Crystal structure of the Abl SH3 domain V73E-A74S-S75R-G76T-D77E-G92N-Y93N-N94T-H95E …	X-RAY DIFFRACTION	1.65
2HZI	Abl kinase domain in complex with PD180970	X-RAY DIFFRACTION	1.7
4J9H	Crystal structure of the ABL-SH3 domain complexed with the designed high-affinity peptide …	X-RAY DIFFRACTION	1.7
4J9B	Crystal structure of the Abl-SH3 domain H59Q-N96T mutant	X-RAY DIFFRACTION	1.7
2O88	Crystal structure of the N114A mutant of ABL-SH3 domain complexed with a designed …	X-RAY DIFFRACTION	1.75
3K2M	Crystal Structure of Monobody HA4/Abl1 SH2 Domain Complex	X-RAY DIFFRACTION	1.75
2G1T	A Src-like Inactive Conformation in the Abl Tyrosine Kinase Domain	X-RAY DIFFRACTION	1.8
3EG2	Crystal structure of the N114Q mutant of ABL-SH3 domain	X-RAY DIFFRACTION	1.8
4J9G	Crystal structure of the ABL-SH3 domain complexed with the designed high-affinity peptide …	X-RAY DIFFRACTION	1.8
3QRJ	The crystal structure of human abl1 kinase domain T315I mutant in complex with DCC-2036	X-RAY DIFFRACTION	1.82
7PVV	Crystal structure of the Abl SH3 domain G92N-Y93N-N94T-H95E mutant	X-RAY DIFFRACTION	1.82
3UYO	Crystal structure of monobody SH13/ABL1 SH2 domain complex	X-RAY DIFFRACTION	1.83
3EG1	Crystal structure of the N114Q mutant of ABL-SH3 domain complexed with a designed …	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00519-F1	64.68	0.39

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, Predicted intracellular proteins, RAS pathway related proteins, Cancer-related genes, Candidate cancer biomarkers, Mutational cancer driver genes, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; nuclear bodies

Antibody reliability (HPA): IH supported · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2)

Position	Role
363	proton acceptor
26–27	breakpoint for translocation to form bcr-abl and nup214-abl1 fusion proteins

Ligand- & substrate-binding residues (3)

Position	Role
248–256	ATP
271	ATP
316–322	ATP

Post-translational modifications (35)

Type	Positions
N-myristoyl glycine	2
Phosphoserine	50, 229, 446, 559, 569, 618, 619, 620, 659, 683, 718, 855, 917, 977
Phosphotyrosine	70, 115, 128, 139, 172, 185, 215, 226, 253, 257, 393, 413
N6-acetyllysine	711
Phosphothreonine	735, 751, 781, 814, 823, 844, 852

Mutagenesis-validated functional residues (1)

Position	Phenotype
735	abolishes phosphorylation. loss of binding ywhas and ywhaz. localizes to the nucleus. no effect on kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

9 curated (TAS) of 53; 7 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

53 pathways:

ID	Pathway	Evidence
R-HSA-9664422	FCGR3A-mediated phagocytosis ⚕	curated
R-HSA-69231	Cyclin D associated events in G1	curated
R-HSA-5685938	HDR through Single Strand Annealing (SSA)	curated
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	curated
R-HSA-5663213	RHO GTPases Activate WASPs and WAVEs	curated
R-HSA-8939236	RUNX1 regulates transcription of genes involved in differentiation of HSCs	curated
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	curated
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation	curated
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9658195	Leishmania infection ⚕	—
R-HSA-9664417	Leishmania phagocytosis ⚕	—
R-HSA-9664407	Parasite infection ⚕	—
R-HSA-9824443	Parasitic Infection Pathways ⚕	—
R-HSA-422475	Axon guidance	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-9855142	Cellular responses to mechanical stimuli	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-5693606	DNA Double Strand Break Response	—
R-HSA-5693532	DNA Double-Strand Break Repair	—
R-HSA-73894	DNA Repair	—
R-HSA-1266738	Developmental Biology	—
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes	—
R-HSA-9851695	Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	—
R-HSA-212165	Epigenetic regulation of gene expression	—
R-HSA-9818564	Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	—
R-HSA-983231	Factors involved in megakaryocyte development and platelet production	electronic
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis	—
R-HSA-69236	G1 Phase	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	—
R-HSA-109582	Hemostasis	—
R-HSA-5693538	Homology Directed Repair	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-453279	Mitotic G1 phase and G1/S transition	—
R-HSA-525793	Myogenesis	electronic
R-HSA-9675108	Nervous system development	—
R-HSA-195258	RHO GTPase Effectors	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-8941326	RUNX2 regulates bone development	—
R-HSA-8940973	RUNX2 regulates osteoblast differentiation	electronic
R-HSA-9860931	Response of endothelial cells to shear stress	—
R-HSA-428890	Role of ABL in ROBO-SLIT signaling	electronic
R-HSA-162582	Signal Transduction	—
R-HSA-376176	Signaling by ROBO receptors	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—
R-HSA-8878171	Transcriptional regulation by RUNX1	—
R-HSA-8878166	Transcriptional regulation by RUNX2	—

MSigDB gene sets: 959 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_DENDRITE_DEVELOPMENT, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS

GO Biological Process (84): mitotic cell cycle (GO:0000278), mismatch repair (GO:0006298), regulation of DNA-templated transcription (GO:0006355), autophagy (GO:0006914), DNA damage response (GO:0006974), response to oxidative stress (GO:0006979), cell adhesion (GO:0007155), epidermal growth factor receptor signaling pathway (GO:0007173), positive regulation of cytosolic calcium ion concentration (GO:0007204), integrin-mediated signaling pathway (GO:0007229), associative learning (GO:0008306), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), response to xenobiotic stimulus (GO:0009410), regulation of autophagy (GO:0010506), positive regulation of endothelial cell migration (GO:0010595), actin cytoskeleton organization (GO:0030036), actin filament polymerization (GO:0030041), regulation of endocytosis (GO:0030100), regulation of cell adhesion (GO:0030155), regulation of axon extension (GO:0030516), phospholipase C-inhibiting G protein-coupled receptor signaling pathway (GO:0030845), regulation of microtubule polymerization (GO:0031113), regulation of Cdc42 protein signal transduction (GO:0032489), regulation of actin cytoskeleton organization (GO:0032956), cellular response to oxidative stress (GO:0034599), response to endoplasmic reticulum stress (GO:0034976), intracellular signal transduction (GO:0035556), platelet-derived growth factor receptor-beta signaling pathway (GO:0035791), protein modification process (GO:0036211), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), neuropilin signaling pathway (GO:0038189), signal transduction in response to DNA damage (GO:0042770), positive regulation of apoptotic process (GO:0043065), positive regulation of neuron apoptotic process (GO:0043525), endothelial cell migration (GO:0043542), regulation of T cell differentiation (GO:0045580), positive regulation of vasoconstriction (GO:0045907), positive regulation of transcription by RNA polymerase II (GO:0045944), ephrin receptor signaling pathway (GO:0048013), positive regulation of fibroblast proliferation (GO:0048146), negative regulation of ubiquitin-protein transferase activity (GO:0051444), myoblast proliferation (GO:0051450), positive regulation of stress fiber assembly (GO:0051496), regulation of cell cycle (GO:0051726), mitochondrial depolarization (GO:0051882), positive regulation of focal adhesion assembly (GO:0051894), cardiac muscle cell proliferation (GO:0060038), cellular response to hydrogen peroxide (GO:0070301), DNA conformation change (GO:0071103), cellular response to transforming growth factor beta stimulus (GO:0071560), response to epinephrine (GO:0071871), positive regulation of cell migration involved in sprouting angiogenesis (GO:0090050), vascular endothelial cell response to oscillatory fluid shear stress (GO:0097706), regulation of postsynaptic specialization assembly (GO:0099150), positive regulation of phospholipase C/protein kinase C signal transduction (GO:0141214), positive regulation of dendrite development (GO:1900006), positive regulation of substrate adhesion-dependent cell spreading (GO:1900026), negative regulation of long-term synaptic potentiation (GO:1900272), regulation of hematopoietic stem cell differentiation (GO:1902036), positive regulation of extracellular matrix organization (GO:1903055)

+24 more (showing top 60).

GO Molecular Function (34): magnesium ion binding (GO:0000287), four-way junction DNA binding (GO:0000400), bubble DNA binding (GO:0000405), phosphotyrosine residue binding (GO:0001784), DNA binding (GO:0003677), transcription coactivator activity (GO:0003713), actin monomer binding (GO:0003785), nicotinate-nucleotide adenylyltransferase activity (GO:0004515), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), protein kinase C binding (GO:0005080), ATP binding (GO:0005524), enzyme activator activity (GO:0008047), kinase activity (GO:0016301), enzyme binding (GO:0019899), syntaxin binding (GO:0019905), manganese ion binding (GO:0030145), neuropilin binding (GO:0038191), SH2 domain binding (GO:0042169), protein serine/threonine kinase activator activity (GO:0043539), ephrin receptor binding (GO:0046875), actin filament binding (GO:0051015), mitogen-activated protein kinase binding (GO:0051019), proline-rich region binding (GO:0070064), delta-catenin binding (GO:0070097), sequence-specific double-stranded DNA binding (GO:1990837), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), protein kinase binding (GO:0019901), protein domain specific binding (GO:0019904), metal ion binding (GO:0046872)

GO Cellular Component (21): ruffle (GO:0001726), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), actin cytoskeleton (GO:0015629), nuclear body (GO:0016604), dendrite (GO:0030425), growth cone (GO:0030426), nuclear membrane (GO:0031965), protein-containing complex (GO:0032991), neuronal cell body (GO:0043025), perinuclear region of cytoplasm (GO:0048471), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), cytoskeleton (GO:0005856), cell leading edge (GO:0031252)

Reactome top-level categories

14 top-level categories:

Category	Pathways
Fcgamma receptor (FCGR) dependent phagocytosis	1
Signaling by ROBO receptors	1
Developmental Biology	1
RHO GTPase Effectors	1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
DNA Double Strand Break Response	1
G1 Phase	1
Transcriptional regulation by RUNX1	1
RUNX2 regulates bone development	1
Leishmania phagocytosis	1
Hemostasis	1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1
Response of endothelial cells to shear stress	1
Immune System	1

GO top-level categories

showing 60 of 86 GO namespaces:

Category	Terms
cellular anatomical structure	5
intracellular membraneless organelle	3
cytoplasm	3
DNA secondary structure binding	2
protein kinase activity	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
synapse	2
cell cycle	1
mitotic nuclear division	1
DNA repair	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
cellular response to stress	1
response to stress	1
cellular process	1
ERBB signaling pathway	1
regulation of biological quality	1
cell surface receptor signaling pathway	1
learning	1
DNA damage response	1
intrinsic apoptotic signaling pathway	1
response to chemical	1
autophagy	1
regulation of catabolic process	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
cytoskeleton organization	1
actin filament-based process	1
actin polymerization or depolymerization	1
protein polymerization	1
endocytosis	1
regulation of transport	1
regulation of cellular component organization	1
cell adhesion	1
regulation of cellular process	1
regulation of developmental growth	1
axon extension	1
regulation of extent of cell growth	1
metal ion binding	1
protein phosphorylated amino acid binding	1
nucleic acid binding	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
actin binding	1
adenylyltransferase activity	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein tyrosine kinase activity	1
protein kinase binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
catalytic activity	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 55 of 139 annotations. The rest are phylogenetic / computational / electronic (IEA).

55 experimentally-supported GO terms:

GO term	NS	Evidence
DNA conformation change	BP	direct assay
DNA damage response	BP	direct assay
cellular response to hydrogen peroxide	BP	direct assay
cellular response to oxidative stress	BP	direct assay
endothelial cell migration	BP	mutant phenotype
integrin-mediated signaling pathway	BP	mutant phenotype
intracellular signal transduction	BP	direct assay
negative regulation of double-strand break repair via homologous recombination	BP	direct assay
negative regulation of ubiquitin-protein transferase activity	BP	direct assay
neuropilin signaling pathway	BP	mutant phenotype
phospholipase C-inhibiting G protein-coupled receptor signaling pathway	BP	mutant phenotype
platelet-derived growth factor receptor-beta signaling pathway	BP	mutant phenotype
positive regulation of apoptotic process	BP	direct assay
positive regulation of cytosolic calcium ion concentration	BP	mutant phenotype
positive regulation of endothelial cell migration	BP	mutant phenotype
positive regulation of focal adhesion assembly	BP	mutant phenotype
positive regulation of phospholipase C/protein kinase C signal transduction	BP	direct assay
positive regulation of stress fiber assembly	BP	mutant phenotype
positive regulation of substrate adhesion-dependent cell spreading	BP	mutant phenotype
protein localization to cytoplasmic microtubule plus-end	BP	mutant phenotype
regulation of Cdc42 protein signal transduction	BP	mutant phenotype
regulation of actin cytoskeleton organization	BP	mutant phenotype
regulation of axon extension	BP	mutant phenotype
regulation of microtubule polymerization	BP	mutant phenotype
response to oxidative stress	BP	genetic interaction
signal transduction in response to DNA damage	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
nuclear body	CC	direct assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
perinuclear region of cytoplasm	CC	direct assay
protein-containing complex	CC	physical interaction
ATP binding	MF	direct assay
SH2 domain binding	MF	physical interaction
bubble DNA binding	MF	direct assay
enzyme activator activity	MF	direct assay
enzyme binding	MF	physical interaction
four-way junction DNA binding	MF	direct assay
kinase activity	MF	mutant phenotype
magnesium ion binding	MF	direct assay
manganese ion binding	MF	direct assay
mitogen-activated protein kinase binding	MF	physical interaction
neuropilin binding	MF	physical interaction
non-membrane spanning protein tyrosine kinase activity	MF	direct assay
phosphotyrosine residue binding	MF	physical interaction
proline-rich region binding	MF	direct assay
protein kinase C binding	MF	physical interaction
protein kinase activity	MF	direct assay
protein serine/threonine kinase activator activity	MF	direct assay
protein serine/threonine kinase activity	MF	mutant phenotype
protein tyrosine kinase activity	MF	direct assay
sequence-specific double-stranded DNA binding	MF	direct assay
syntaxin binding	MF	physical interaction

Protein interactions and networks

STRING

showing 16 of 3,972 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABL1	BCR	P11274	974
ABL1	EVPL	Q92817	958
ABL1	ETV6	P41212	880
ABL1	IKZF1	Q13422	850
ABL1	NUP214	P35658	839
ABL1	AFF1	P51825	818
ABL1	TLX1	P31314	752
ABL1	RUNX1	Q01196	751
ABL1	ABI1	Q8IZP0	744
ABL1	CD34	P28906	741
ABL1	PBX1	P40424	741
ABL1	TLX3	O43711	738
ABL1	CDKN2A	P42771	723
ABL1	TP53	P04637	722
ABL1	PIK3CA	P42336	703
ABL1	STAT5B	P51692	703

IntAct

Human interaction partners of ABL1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 229 partners by confidence:

Partner	Interaction type	MIscore	Records
ABI1	physical association	0.900	11
YWHAG	physical association	0.890	1
MSH5	physical association	0.820	9
RIN1	physical association	0.790	6
YWHAE	physical association	0.760	2
CRK	physical association	0.740	5
CRKL	phosphorylation reaction	0.740	3
YWHAB	association	0.730	1
YWHAZ	physical association	0.710	1
ATM	physical association	0.700	4
EGFR	physical association	0.690	3
SFN	physical association	0.670	2
ERCC6	direct interaction	0.660	8
RAPGEF1	physical association	0.660	4
MUC1	physical association	0.650	8
ABI2	physical association	0.640	2
TOP1	physical association	0.600	7
VAV1	physical association	0.600	5
SNCA	physical association	0.600	3
TLN2	physical association	0.600	3
MAVS	physical association	0.590	6
LRRK1	association	0.590	3
SRC	physical association	0.590	2
WASF2	direct interaction	0.590	1
MAP4K1	physical association	0.570	3
WASF1	direct interaction	0.570	3
STAT5B	direct interaction	0.560	2
TP53	direct interaction	0.560	2
SORBS3	direct interaction	0.540	6
ADAM10	direct interaction	0.540	2

BioGRID (583 interactions; top human partners by supporting records): CBL (Biochemical Activity; 22 records), CRK (Biochemical Activity; 15 records), CRKL (Affinity Capture-Western; 14 records), GRB2 (Reconstituted Complex; 12 records), ATM (Biochemical Activity; 10 records), PARK2 (Affinity Capture-MS; 10 records), DOK1 (Reconstituted Complex; 9 records), RB1 (Reconstituted Complex; 8 records), YWHAG (Affinity Capture-MS; 8 records), YWHAZ (Affinity Capture-MS; 8 records), ABI2 (Affinity Capture-Western; 7 records), MSH5 (Affinity Capture-Western; 7 records), PIK3R1 (Reconstituted Complex; 7 records), SHC1 (Affinity Capture-Western; 7 records), YWHAH (Affinity Capture-MS; 7 records)

SIGNOR signaling

showing 47 of 200 signaling interactions:

A	Effect	B	Mechanism
ABL1	“up-regulates activity”	CAT	phosphorylation
ABL1	“up-regulates activity”	GPX1	phosphorylation
PSTPIP1	down-regulates	ABL1
ABL1	down-regulates	EPHB2	phosphorylation
NCK1	“down-regulates activity”	ABL1	binding
ABL1	“up-regulates activity”	ABL1	phosphorylation
ABL1	up-regulates	VAV1	phosphorylation
ABL1	up-regulates	APBB1	phosphorylation
ABL1	up-regulates	LASP1	phosphorylation
ABL1	down-regulates	YTHDC1	phosphorylation
ABL1	up-regulates	CASP9	phosphorylation
ABL1	up-regulates	ABL2	phosphorylation
ABL1	unknown	RB1	phosphorylation
ABL1	down-regulates	PSMA7	phosphorylation
ABL1	up-regulates	EGFR	phosphorylation
ABL1	up-regulates	DDX5	phosphorylation
PAK2	down-regulates	ABL1	phosphorylation
ABL1	up-regulates	YAP1	phosphorylation
ABL1	up-regulates	ESR1	phosphorylation
ABL1	unknown	RAPGEF1	phosphorylation
ABL1	unknown	LGALS3	phosphorylation
CBL	“down-regulates quantity by destabilization”	ABL1	ubiquitination
ABL1	up-regulates	ATR	phosphorylation
ABL1	down-regulates	PRKN	phosphorylation
ABL1	up-regulates	MYLK	phosphorylation
ABL1	down-regulates	MDM2	phosphorylation
ABL1	up-regulates	ABI1	phosphorylation
ABL1	“down-regulates activity”	CRK	phosphorylation
ABL1	down-regulates	CRKL
ABL1	up-regulates	NCOA3	phosphorylation
CLK1	down-regulates	ABL1	phosphorylation
CLK4	down-regulates	ABL1	phosphorylation
STK3	down-regulates	ABL1	phosphorylation
STK4	down-regulates	ABL1	phosphorylation
TTK	down-regulates	ABL1	phosphorylation
ABL1	down-regulates	PDGFRB	phosphorylation
ABL1	up-regulates	RACK1	phosphorylation
CDON	“up-regulates activity”	ABL1	binding
SPAG9	unknown	ABL1	binding
ABL1	up-regulates	CEBPB	phosphorylation
AT9283	down-regulates	ABL1	“chemical inhibition”
bosutinib	down-regulates	ABL1	“chemical inhibition”
“dasatinib (anhydrous)”	down-regulates	ABL1	“chemical inhibition”
DCC-2036	down-regulates	ABL1	“chemical inhibition”
imatinib	down-regulates	ABL1	“chemical inhibition”
“imatinib methanesulfonate”	down-regulates	ABL1	“chemical inhibition”
[4-[2-(1H-indazol-3-yl)ethenyl]phenyl]-(1-piperazinyl)methanone	down-regulates	ABL1	“chemical inhibition”

Protein complexes (CORUM) (22)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

22 complexes by size:

Complex	Subunits	Members
★ ABL1-BCR-(BCR-ABL fusion kinase)-MAP2K1-MAP2K2 complex	5	ABL1, BCR, BCR/ABL fusion, MAP2K1, MAP2K2
★ ABL1-BCR-MAP2K1-MAP2K2 complex	4	BCR, MAP2K1, MAP2K2, ABL1
★ BCR-ABL1(fusion kinase)-SHC1 complex	3	ABL1, BCR, SHC1
★ NUP214-ABL1(fusion kinase)-NUP155 complex	3	ABL1, NUP155, NUP214
★ NUP214-ABL1(fusion kinase)-SMC4 complex	3	ABL1, NUP214, SMC4
★ NUP214-ABL1(fusion kinase)-MAD2L1 complex	3	NUP214, ABL1, MAD2L1
★ NUP214-ABL1(fusion kinase)-STAT1 complex	3	ABL1, NUP214, STAT1
★ BCR-ABL1(fusion kinase)-GRB2 complex	3	ABL1, BCR, GRB2
★ BCR-ABL1(fusion kinase)-CBL complex	3	ABL1, BCR, CBL
★ ABL1-CTTN-MYLK complex	3	CTTN, MYLK, ABL1
★ ABI1-ABL1-BCAR1 complex	3	ABI1, ABL1, BCAR1
★ ABL1-CFL1 complex	2	ABL1, CFL1
★ ABL1-ARHGDIB complex	2	ABL1, ARHGDIB
★ ABL1-TPM3 complex	2	ABL1, TPM3
★ ABL1-PREX2 complex	2	PREX2, ABL1
★ ABL1-TPM2 complex	2	ABL1, TPM2
★ ABL1-TPM1 complex	2	ABL1, TPM1
★ ABL1-VCL complex	2	ABL1, VCL
★ ABL1-YWHAE complex	2	ABL1, YWHAE
★ ABL1-MYBPC1 complex	2	ABL1, MYBPC1
★ ABL1-ACTN2 complex	2	ABL1, ACTN2
★ ABL1-BRCA1 complex	2	ABL1, BRCA1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 229 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	8	29.2×	2e-08
Signaling by FLT3 ITD and TKD mutants	6	24.8×	7e-06
Regulation of signaling by CBL	9	24.3×	2e-08
PI3K events in ERBB2 signaling	6	21.9×	1e-05
Downstream signal transduction	10	20.7×	2e-08
GAB1 signalosome	6	20.7×	1e-05
Activation of BAD and translocation to mitochondria	5	20.7×	1e-04
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	7	19.8×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of Rac protein signal transduction	6	17.6×	3e-04
megakaryocyte development	5	15.9×	1e-03
Fc-gamma receptor signaling pathway involved in phagocytosis	5	15.9×	1e-03
peptidyl-tyrosine phosphorylation	8	15.2×	4e-05
cellular response to gamma radiation	5	13.6×	2e-03
response to gamma radiation	5	13.2×	3e-03
epidermal growth factor receptor signaling pathway	11	12.3×	3e-06
natural killer cell mediated cytotoxicity	6	11.7×	1e-03

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

ABL1 is most relevant to cancer in its role in the BCR-ABL fusion protein that has become a signature of chronic myeloid leukemia (CML). Cells harboring this fusion have shown sensitivity to imatinib, greatly improving the prognostic outlook of the disease. However, additional mutations in ABL1 have been shown to confer resistance to imatinib. In these resistance cases, second-generation tyrosine kinase inhibitors such as dasatinib and nilotinib have exhibited some efficacy and are currently undergoing clinical trials for treating acquired resistance in CML.

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — UCEC.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for ABL1: 959 ClinVar records (25 pathogenic / likely pathogenic); 68 CIViC cancer variants; 6 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

959 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	12
Uncertain significance	319
Likely benign	416
Benign	82

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 25 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
374794	NM_005157.6(ABL1):c.1009G>A (p.Ala337Thr)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
917884	NM_005157.6(ABL1):c.689C>T (p.Pro230Leu)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
983211	NM_005157.6(ABL1):c.1297G>A (p.Ala433Thr)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
987880	NM_005157.6(ABL1):c.295T>C (p.Trp99Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1803095	NM_005157.6(ABL1):c.1511A>G (p.Asp504Gly)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1184856	NM_005157.6(ABL1):c.1388G>A (p.Gly463Asp)	Pathogenic	criteria provided, single submitter	2
376084	NM_005157.6(ABL1):c.730A>G (p.Met244Val)	Pathogenic	criteria provided, single submitter	1
4884467	NM_005157.6(ABL1):c.297G>T (p.Trp99Cys)	Pathogenic	criteria provided, single submitter	1
1029154	NM_005157.6(ABL1):c.2351C>T (p.Pro784Leu)	Likely pathogenic	criteria provided, single submitter	1
1699204	NM_005157.6(ABL1):c.143G>C (p.Trp48Ser)	Likely pathogenic	criteria provided, single submitter	1
2441840	NM_005157.6(ABL1):c.875A>T (p.Glu292Val)	Likely pathogenic	criteria provided, single submitter	1
3062320	NM_005157.6(ABL1):c.1088A>C (p.Asp363Ala)	Likely pathogenic	criteria provided, single submitter	1
3340737	NM_005157.6(ABL1):c.1025A>G (p.Tyr342Cys)	Likely pathogenic	criteria provided, single submitter	1
4527100	NM_005157.6(ABL1):c.403A>G (p.Asn135Asp)	Likely pathogenic	criteria provided, single submitter	1
3063094	GRCh37/hg19 9q34.11-34.13(chr9:131815597-134209182)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ABL1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 1,171):

Position(s)	Effect	Δscore	Sites
9:130835526–130835527	donor_loss	1.0000	4
9:130854042	acceptor_gain	1.0000
9:130854238–130854239	donor_loss	1.0000	5
9:130854799–130854800	acceptor_loss	1.0000	4
9:130872124	acceptor_gain	1.0000
9:130872127–130872128	acceptor_loss	1.0000	6
9:130872214–130872215	donor_loss	1.0000	5
9:130872854	acceptor_gain	1.0000
9:130872858–130872859	acceptor_loss	1.0000	6
9:130873038–130873039	donor_loss	1.0000	5

AlphaMissense

3,101 missense substitutions predicted likely pathogenic (of 7,361 scored), across 631 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M290	9	0.985	1.000
M351	9	0.978	0.999
M278	9	0.973	0.999
M472	9	0.972	0.999
M458	9	0.966	0.999
M318	9	0.962	0.998
M244	9	0.951	0.999
M388	9	0.897	0.996
H173	8	1.000	1.000
D363	8	1.000	1.000
N368	8	1.000	1.000
D381	8	1.000	1.000
H361	8	0.999	1.000
F401	8	0.999	1.000
D421	8	0.999	1.000
H202	8	0.998	1.000
F382	8	0.998	1.000
F416	8	0.998	1.000
H129	8	0.997	1.000
F283	8	0.997	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000276

Disease associations

OMIM: gene MIM:189980 | disease phenotypes: MIM:617602, MIM:608232

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
congenital heart defects and skeletal malformations syndrome	Strong	Autosomal dominant	3
connective tissue disorder	Moderate	Autosomal dominant
bone development disease	Limited	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
DDG2P	green
Familial non syndromic congenital heart disease	green
Fetal anomalies	green
Paediatric disorders - additional genes	green
Thoracic aortic aneurysm or dissection	green
Thoracic aortic aneurysm or dissection (GMS)	green
Ehlers Danlos syndrome with a likely monogenic cause	amber
Limb disorders	amber
Paediatric disorders	amber
Skeletal dysplasia	amber

Mondo (8): congenital heart defects and skeletal malformations syndrome (MONDO:0060532), chronic myeloid leukemia (MONDO:0011996), congenital heart disease (MONDO:0005453), lip and oral cavity carcinoma (MONDO:0023644), T-cell acute lymphoblastic leukemia (MONDO:0004963), microcephaly (MONDO:0001149), bone development disease (MONDO:0005497), connective tissue disorder (MONDO:0003900)

Orphanet (3): Marfanoid habitus-facial dysmorphism-skeletal abnormality-heart defect syndrome (Orphanet:643503), Chronic myeloid leukemia (Orphanet:521), Moyamoya angiopathy (Orphanet:477768)

HPO phenotypes

showing 60 of 62 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000218	High palate
HP:0000233	Thin vermilion border
HP:0000307	Pointed chin
HP:0000319	Smooth philtrum
HP:0000331	Short chin
HP:0000337	Broad forehead
HP:0000341	Narrow forehead
HP:0000460	Narrow nose
HP:0000490	Deeply set eye
HP:0000582	Upslanted palpebral fissure
HP:0000670	Carious teeth
HP:0000678	Dental crowding
HP:0000767	Pectus excavatum
HP:0000776	Congenital diaphragmatic hernia
HP:0000963	Thin skin
HP:0000965	Cutis marmorata
HP:0000977	Soft skin
HP:0001166	Arachnodactyly
HP:0001263	Global developmental delay
HP:0001382	Joint hypermobility
HP:0001442	Typified by somatic mosaicism
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001680	Coarctation of aorta
HP:0001744	Splenomegaly
HP:0001763	Pes planus
HP:0001852	Sandal gap
HP:0001871	Abnormality of blood and blood-forming tissues
HP:0001873	Thrombocytopenia
HP:0001894	Thrombocytosis
HP:0001911	Abnormal granulocyte morphology
HP:0001912	Abnormal basophil morphology
HP:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0002007	Frontal bossing
HP:0002010	Narrow maxilla
HP:0002023	Anal atresia
HP:0002566	Intestinal malrotation
HP:0002616	Aortic root aneurysm
HP:0002650	Scoliosis
HP:0002714	Downturned corners of mouth
HP:0002808	Kyphosis
HP:0003189	Long nose
HP:0003196	Short nose
HP:0003577	Congenital onset
HP:0004209	Clinodactyly of the 5th finger
HP:0004322	Short stature
HP:0004396	Poor appetite
HP:0004848	Ph-positive acute lymphoblastic leukemia
HP:0004852	Reduced leukocyte alkaline phosphatase
HP:0005506	Chronic myelogenous leukemia
HP:0005547	Myeloproliferative disorder
HP:0006522	Repeated pneumothoraces
HP:0010747	Medial flaring of the eyebrow
HP:0012378	Fatigue

GWAS associations

6 associations:

Study	Trait	p-value
GCST90002402_19	Platelet count	7e-13
GCST90002407_195	White blood cell count	8e-12
GCST90002388_516	Lymphocyte count	9e-11
GCST90002404_371	Red cell distribution width	1e-10
GCST005174_30	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	5e-6
GCST001651_24	Response to amphetamines	8e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0004587	lymphocyte count
EFO:0004309	platelet count
EFO:0009188	Red cell distribution width

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (13): CHEMBL1862 (SINGLE PROTEIN), CHEMBL2096618 (CHIMERIC PROTEIN), CHEMBL2111414 (PROTEIN FAMILY), CHEMBL3885630 (PROTEIN-PROTEIN INTERACTION), CHEMBL3885645 (CHIMERIC PROTEIN), CHEMBL4296119 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296120 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296137 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523725 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523750 (PROTEIN-PROTEIN INTERACTION)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the ABL1 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

18 curated-mechanism drugs:

Drug	Modality	Max phase
ASCIMINIB	Small molecule	4
BOSUTINIB	Small molecule	4
DASATINIB ANHYDROUS	Small molecule	4
IMATINIB MESYLATE	Small molecule	4
NILOTINIB HYDROCHLORIDE MONOHYDRATE	Small molecule	4
REGORAFENIB	Small molecule	4
UMBRALISIB TOSYLATE	Small molecule	4
FLUMATINIB	Small molecule	3
RUSERONTINIB	Small molecule	3
SARACATINIB	Small molecule	3
AT-9283	Small molecule	2
AZM-475271	Small molecule	2
BAFETINIB	Small molecule	2
REBASTINIB	Small molecule	2
VODOBATINIB	Small molecule	2
AZD-0424	Small molecule	1
KW-2449	Small molecule	1
XL-228	Small molecule	1

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes ABL1 — the drug acts on the assembly or class, not necessarily on this subunit alone.

3 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
PONATINIB HYDROCHLORIDE	Bcr/Abl fusion protein	2	4
OLVEREMBATINIB	Bcr/Abl fusion protein	2	3
RADOTINIB	Bcr/Abl fusion protein	2	3

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,105,865 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 122 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL4208229	ASCIMINIB	4	946
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL5416410	DASATINIB	4	674
CHEMBL1421	DASATINIB ANHYDROUS	4	55,947
CHEMBL941	IMATINIB	4	113,105
CHEMBL1642	IMATINIB MESYLATE	4	70,926
CHEMBL255863	NILOTINIB	4	39,362
CHEMBL1946170	REGORAFENIB	4	13,318
CHEMBL1173655	AFATINIB	4	15,878
CHEMBL2105712	AFATINIB DIMALEATE	4	3,441
CHEMBL1289926	AXITINIB	4	16,510
CHEMBL857	BIOTIN	4	590,540
CHEMBL3545311	BRIGATINIB	4	5,988
CHEMBL2105717	CABOZANTINIB	4	11,799
CHEMBL2403108	CERITINIB	4	9,002
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL2028663	DABRAFENIB	4	13,060
CHEMBL1983268	ENTRECTINIB	4	3,737
CHEMBL553	ERLOTINIB	4	109,860
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL3301607	FILGOTINIB	4
CHEMBL939	GEFITINIB	4
CHEMBL1873475	IBRUTINIB	4
CHEMBL1852688	INFIGRATINIB	4
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4
CHEMBL554	LAPATINIB	4
CHEMBL1289601	LENVATINIB	4
CHEMBL685	MEBENDAZOLE	4
CHEMBL608533	MIDOSTAURIN	4
CHEMBL180022	NERATINIB	4
CHEMBL502835	NINTEDANIB	4
CHEMBL477772	PAZOPANIB	4
CHEMBL1171837	PONATINIB	4
CHEMBL576982	QUIZARTINIB	4
CHEMBL1789941	RUXOLITINIB	4
CHEMBL1336	SORAFENIB	4
CHEMBL535	SUNITINIB	4
CHEMBL571546	TIRBANIBULIN	4
CHEMBL1289494	TIVOZANIB	4
CHEMBL221959	TOFACITINIB	4
CHEMBL2103743	TOFACITINIB CITRATE	4
CHEMBL3348923	TOVORAFENIB	4
CHEMBL24828	VANDETANIB	4
CHEMBL3545413	FLUMATINIB	3
CHEMBL217092	SARACATINIB	3
CHEMBL483158	ALISERTIB	3
CHEMBL428690	ALVOCIDIB	3
CHEMBL377300	BRIVANIB	3
CHEMBL31965	CANERTINIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL3137331	DEFACTINIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL1908391	MASITINIB	3
CHEMBL572881	MOTESANIB	3
CHEMBL2316582	OLVEREMBATINIB	3
CHEMBL4297524	RADOTINIB	3
CHEMBL165	RESVERATROL	3
CHEMBL276711	SEMAXANIB	3

Clinical evidence (CIViC)

Drug × variant × indication, from 435 curated evidence items; also 1 prognostic. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

showing 30 of 288 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
BCR::ABL1 Fusion AND ABL1 T315I	Ponatinib	B-lymphoblastic Leukemia/lymphoma	Sensitivity/Response	CIViC A	EID11236
BCR::ABL1 Fusion AND ABL1 T315I	Ponatinib	Chronic Myeloid Leukemia	Sensitivity/Response	CIViC B	EID1390 +2
BCR::ABL1 Fusion AND ABL1 M351T	Bosutinib	Chronic Myeloid Leukemia	Sensitivity/Response	CIViC B	EID4393 +1
BCR::ABL1 Fusion AND ABL1 T315I	Omacetaxine Mepesuccinate	Chronic Myeloid Leukemia	Sensitivity/Response	CIViC B	EID6197 +1
BCR::ABL1 Fusion AND ABL1 F317L	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID6309 +6
BCR::ABL1 Fusion AND ABL1 T315I	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID4365 +5
BCR::ABL1 Fusion AND ABL1 T315I	Imatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID234 +4
BCR::ABL1 Fusion AND ABL1 Y253H	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID4335 +3
BCR::ABL1 Fusion AND ABL1 E255V	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID4447 +2
BCR::ABL1 Fusion AND ABL1 E355G	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID4403 +2
BCR::ABL1 Fusion AND ABL1 F359V	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID3819 +2
BCR::ABL1 Fusion AND ABL1 M244V	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID4302 +2
BCR::ABL1 Fusion AND ABL1 M351T	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID4396 +2
ABL1 Non-P-Loop Mutation	Bosutinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID6337 +1
ABL1 P-Loop Mutation	Bosutinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID6336 +1
ABL1 TKD Mutation	Bosutinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID6335 +1
BCR::ABL1 Fusion AND ABL1 E255K	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID4350 +1
BCR::ABL1 Fusion AND ABL1 E459K	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID6310 +1
BCR::ABL1 Fusion AND ABL1 F359I	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID4532 +1
BCR::ABL1 Fusion AND ABL1 F486S	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID4571 +1
BCR::ABL1 Fusion AND ABL1 G250E	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID4316 +1
BCR::ABL1 Fusion AND ABL1 G250E	Imatinib Mesylate	Chronic Myeloid Leukemia	Resistance	CIViC B	EID7041 +1
BCR::ABL1 Fusion AND ABL1 H396R	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID4413 +1
BCR::ABL1 Fusion AND ABL1 L248V	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID6308 +1
BCR::ABL1 Fusion AND ABL1 Y253H	Imatinib Mesylate	Chronic Myeloid Leukemia	Resistance	CIViC B	EID7040 +1
ABL1 TKD Mutation	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID6311
ABL1 TKD Mutation	Nilotinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID6342
BCR::ABL1 Fusion AND ( ABL1 F317L OR ABL1 F317V )	Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID4386
BCR::ABL1 Fusion AND ABL1 V299L	Imatinib Mesylate	Chronic Myeloid Leukemia	Resistance	CIViC B	EID6982
BCR::ABL1 Fusion AND ABL1 H396R	Dasatinib	Chronic Myeloid Leukemia	Sensitivity/Response	CIViC C	EID4414 +3

CIViC column: a representative evidence item (EID); +N = additional CIViC items supporting the same association.

CIViC curated variants (68)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

G250E (missense variant), F317L (missense variant), M351T (missense variant), E292V (missense variant), L384M (missense variant), L387F (missense variant), G398R (missense variant), L387M (missense variant), S438C (missense variant), L298V (missense variant), F311I (missense variant), L364I (missense variant), E453Q (missense variant), M343T (missense variant), F317V (missense variant), E279K (missense variant), Q300R (missense variant), F311L (missense variant), N331S (missense variant), L364P (missense variant), H396P (missense variant), E450V (missense variant), E453K (missense variant), E453A (missense variant), P480A (missense variant), V289I (missense variant), V379I (missense variant), M388L (missense variant), S417Y (missense variant), E450Q (missense variant), F317I (missense variant), C475V (splice donor variant), N336S (missense variant), R351W (missense variant), G340L (coding sequence variant), T315I (missense variant), L248R (missense variant), F317S (missense variant), F317C (missense variant), E459K (missense variant), TKD Mutation, P-Loop Mutation, Non-P-Loop Mutation, T315V (missense variant), E292L (missense variant), F317R (missense variant), E98G (missense variant), N146S (missense variant), E255K (missense variant), Double Ph, D276G (missense variant), Y253H (missense variant), M244V (missense variant), F359V (missense variant), E255V (missense variant), F359I (missense variant), E355G (missense variant), F359C (missense variant), H396R (missense variant), L248V (missense variant) …(+8 more).

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs121913459	dasatinib	Other, Metabolism/PK	Genotype CT is associated with decreased AUC 0-4 hours of dasatinib in people with Leukemia as compared to genotype CC.	PMID:22587422

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Abl family

Most potent curated ligand interactions (31 total), top 25:

Ligand	Action	Affinity	Parameter
dasatinib	Inhibition	10.49	pKd
compound 8h [PMID: 21561767]	Inhibition	9.7	pIC50
asciminib	Negative	9.52	pIC50
olverembatinib	Inhibition	9.47	pIC50
SIAIS178	Inhibition	9.46	pKd
embibatinib	Inhibition	9.42	pIC50
vamotinib	Inhibition	9.31	pIC50
compound 24 [PMID: 23441572]	Inhibition	9.3	pIC50
rebastinib	Inhibition	9.1	pIC50
bosutinib	Inhibition	9.0	pIC50
compound 2c [PMID: 24900538]	Inhibition	8.92	pIC50
flumbatinib	Inhibition	8.92	pIC50
meribatinib	Inhibition	8.53	pIC50
pexmetinib	Inhibition	8.4	pIC50
PD-173955	Inhibition	8.3	pIC50
bafetinib	Inhibition	8.24	pIC50
ponatinib	Inhibition	8.1	pIC50
KW-2449	Inhibition	7.85	pIC50
ZAK inhibitor 6p	Inhibition	7.82	pKd
nilotinib	Inhibition	7.8	pIC50
PP121	Inhibition	7.74	pIC50
saracatinib	Inhibition	7.52	pIC50
compound 33a [PMID: 35944901]	Inhibition	7.36	pIC50
relcobatinib	Inhibition	7.36	pIC50
BO1	Inhibition	7.36	pKi

Binding affinities (BindingDB)

3556 measured of 4305 human assays (4402 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL2347725	IC50	0.015 nM
cis-(1S,2S)-2-fluoro-N-[7-(5-fluoro-4-methyl-3-pyridinyl)isoquinolin-3-yl]cyclopropane-1-carboxamide	KI	0.0186 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(5-hydroxy-2-methylphenyl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.02 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
2-fluoro-N-[7-(4-methyl-3-pyridinyl)isoquinolin-3-yl]cyclopropane-1-carboxamide	KI	0.02 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(5-fluoro-4-methyl-3-pyridinyl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.02 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-[6-(hydroxymethyl)-4-methyl-3-pyridinyl]isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.02 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-[5-fluoro-6-(hydroxymethyl)-4-methyl-3-pyridinyl]isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.02 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
(2S)-2-fluoro-N-[7-[4-methyl-6-[(1S)-2,2,2-trifluoro-1-hydroxyethyl]-3-pyridinyl]isoquinolin-3-yl]cyclopropane-1-carboxamide	KI	0.02 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
cis-(1S,2S)-2-fluoro-N-[7-(5-methyl-1H-indazol-4-yl)-2,6-naphthyridin-3-yl]cyclopropane-1-carboxamide	KI	0.02 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
CHEMBL1221411	KI	0.02 nM
CHEMBL2347722	IC50	0.021 nM
N-[7-(4-methyl-3-pyridinyl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.03 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(3-hydroxy-2-methylphenyl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.03 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(4-fluoro-5-hydroxy-2-methylphenyl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.03 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-[5-(hydroxymethyl)-2-methylphenyl]isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.03 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(5-methyl-1H-indazol-4-yl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.03 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-[4-methyl-6-[(1S)-2,2,2-trifluoro-1-hydroxyethyl]-3-pyridinyl]isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.03 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-[4-methyl-6-[(1R)-2,2,2-trifluoro-1-hydroxyethyl]-3-pyridinyl]isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.03 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
(2R)-2-fluoro-N-[7-(4-methyl-3-pyridinyl)isoquinolin-3-yl]cyclopropane-1-carboxamide	KI	0.03 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
(2S)-2-fluoro-N-[7-(4-methyl-3-pyridinyl)isoquinolin-3-yl]cyclopropane-1-carboxamide	KI	0.03 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
CHEMBL2347711	IC50	0.03 nM
N-[7-(2-chloro-5-hydroxyphenyl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.04 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(1H-indazol-4-yl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.04 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(5-hydroxy-4-methyl-3-pyridinyl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.04 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(5-methyl-1H-pyrazolo[3,4-c]pyridin-4-yl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.04 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
CHEMBL3808884	EC50	0.04 nM
N-[7-[6-[(1R)-1-hydroxyethyl]-4-methyl-3-pyridinyl]isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.05 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-[6-[(1S)-1-hydroxyethyl]-4-methyl-3-pyridinyl]isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.05 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
cis-(1S,2S)-2-fluoro-N-[7-(4-methyl-3-pyridinyl)isoquinolin-3-yl]cyclopropane-1-carboxamide	KI	0.05 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide	EC50	0.05 nM
N-[7-(2-cyano-4-fluorophenyl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.06 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
cis-(1R,2R)-2-fluoro-N-[7-(4-methyl-3-pyridinyl)isoquinolin-3-yl]cyclopropane-1-carboxamide	KI	0.06 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
CHEMBL2347710	IC50	0.06 nM
CHEMBL6159841	IC50	0.06 nM
CHEMBL5282076	KI	0.062 nM
CHEMBL2347723	IC50	0.064 nM
N-[7-(2-cyano-4,5-difluorophenyl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.07 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(4-chloro-3-pyridinyl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.07 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-[2-(hydroxymethyl)-4-methyl-3-pyridinyl]isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.07 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(2-fluoro-6-methylphenyl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.0709 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(2H-benzotriazol-4-yl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.0723 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
(2S)-2-fluoro-N-[7-[(2R)-2-methyl-5-oxopyrrolidin-1-yl]isoquinolin-3-yl]cyclopropane-1-carboxamide	KI	0.0799 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
(2S)-2-fluoro-N-[7-[(2S)-2-methyl-5-oxopyrrolidin-1-yl]isoquinolin-3-yl]cyclopropane-1-carboxamide	KI	0.0799 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(5-fluoro-2-methylphenyl)-5-methyl-2,6-naphthyridin-3-yl]cyclopropanecarboxamide	KI	0.08 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
(2S)-N-[7-[5-chloro-4-methyl-6-[(1R)-2,2,2-trifluoro-1-hydroxyethyl]-3-pyridinyl]isoquinolin-3-yl]-2-fluorocyclopropane-1-carboxamide	KI	0.0841 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
(2S)-N-[7-[5-chloro-4-methyl-6-[(1S)-2,2,2-trifluoro-1-hydroxyethyl]-3-pyridinyl]isoquinolin-3-yl]-2-fluorocyclopropane-1-carboxamide	KI	0.0841 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[(7E)-7-(1-hydroxy-3-methyl-2-pyridinylidene)isoquinolin-3-ylidene]cyclopropanecarboxamide	KI	0.0896 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
(2S)-2-fluoro-N-[7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl]cyclopropane-1-carboxamide	KI	0.09 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
(2R)-2-fluoro-N-[7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl]cyclopropane-1-carboxamide	KI	0.09 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(4-fluoro-3-hydroxyphenyl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.09 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.82	IC50	0.015	nM	CHEMBL2347725
10.80	IC50	0.016	nM	DASATINIB
10.80	Kd	0.016	nM	DASATINIB
10.73	Ki	0.0186	nM	CHEMBL3689722
10.72	Kd	0.019	nM	DASATINIB
10.70	Ki	0.02	nM	CHEMBL3685056
10.70	Ki	0.02	nM	CHEMBL3685101
10.70	Ki	0.02	nM	CHEMBL3639840
10.70	Ki	0.02	nM	CHEMBL3685180
10.70	Ki	0.02	nM	CHEMBL3689554
10.70	Ki	0.02	nM	CHEMBL3689631
10.70	Ki	0.02	nM	CHEMBL3689678
10.70	Ki	0.02	nM	CHEMBL577269
10.70	Ki	0.02	nM	CHEMBL1221411
10.68	IC50	0.021	nM	CHEMBL2347722
10.60	Kd	0.025	nM	DASATINIB
10.54	Kd	0.029	nM	DASATINIB
10.54	Kd	0.029	nM	BOSUTINIB
10.52	Ki	0.03	nM	CHEMBL3685020
10.52	Ki	0.03	nM	CHEMBL3685089
10.52	Ki	0.03	nM	CHEMBL3685095
10.52	Ki	0.03	nM	CHEMBL3685096
10.52	Ki	0.03	nM	CHEMBL3689574
10.52	Ki	0.03	nM	CHEMBL3689596
10.52	Ki	0.03	nM	CHEMBL3689597
10.52	Ki	0.03	nM	CHEMBL3689608
10.52	Ki	0.03	nM	CHEMBL3689609
10.52	IC50	0.03	nM	CHEMBL2347711
10.52	Ki	0.03	nM	DASATINIB
10.49	Kd	0.032	nM	DASATINIB
10.44	Kd	0.036	nM	BOSUTINIB
10.43	Kd	0.037	nM	DASATINIB
10.43	Kd	0.037	nM	BOSUTINIB
10.41	Kd	0.039	nM	BOSUTINIB
10.40	EC50	0.04	nM	CHEMBL3808884
10.40	EC50	0.04	nM	DASATINIB
10.40	Ki	0.04	nM	CHEMBL3685023
10.40	Ki	0.04	nM	CHEMBL3685134
10.40	Ki	0.04	nM	CHEMBL3685179
10.40	Ki	0.04	nM	CHEMBL3689575
10.39	Kd	0.041	nM	DASATINIB
10.34	Kd	0.046	nM	DASATINIB
10.33	Kd	0.047	nM	DASATINIB
10.33	Kd	0.047	nM	BOSUTINIB
10.30	EC50	0.05	nM	PONATINIB
10.30	Ki	0.05	nM	CHEMBL3689567
10.30	Ki	0.05	nM	CHEMBL3689568
10.30	Ki	0.05	nM	CHEMBL3689578
10.24	Kd	0.058	nM	DASATINIB
10.24	Kd	0.057	nM	BOSUTINIB

PubChem BioAssay actives

2288 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-(3-aminoanilino)-6-(2,6-dichlorophenyl)-8-methylpyrido[2,3-d]pyrimidin-7-one	501985: Inhibition of recombinant c-Abl after 30 mins	ki	<0.0001	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	1301834: Inhibition of human wild type BCR-ABL expressed in mouse BAF3 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay	ec50	<0.0001	uM
Dasatinib	1801731: Kinome-Wide Inhibitor Profiling from Article 10.1021/acschembio.5b01018: “Conformation-Selective Analogues of Dasatinib Reveal Insight into Kinase Inhibitor Binding and Selectivity.”	kd	<0.0001	uM
2-[[6-[4-[2-[2-(2-aminoethoxy)ethoxy]ethyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide	1515650: Binding affinity to ABL (unknown origin) by TR-FRET assay	ki	0.0001	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-[3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)propanoyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1801732: End Point Fluorescence Assay from Article 10.1021/acschembio.5b01018: “Conformation-Selective Analogues of Dasatinib Reveal Insight into Kinase Inhibitor Binding and Selectivity.”	kd	0.0001	uM
4-(2-chloro-5-methoxyanilino)-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile	2236715: Inhibition of wild-type Bcr-Abl (unknown origin) in presence of ATP	ic50	0.0001	uM
2-(dimethylamino)ethyl 4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazine-1-carboxylate	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0001	uM
2-[2-[2-[2-[2-[2-[6-[4-[3-[3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxyquinolin-7-yl]oxypropyl]piperazin-1-yl]hexoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]acetamide	1678549: Protac binding affinity at CRBN/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0001	uM
2-[2-[6-[4-[3-[3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxyquinolin-7-yl]oxypropyl]piperazin-1-yl]hexoxy]ethoxy]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]acetamide	1678549: Protac binding affinity at CRBN/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0001	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-[6-[2-[2-[2-[2-[2-[2-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]hexyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1678553: Protac binding affinity at VHL/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0001	uM
4-chloro-2-[5-methyl-3-[4-(3-pyrrolidin-1-ylpropoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1958839: Binding affinity to Abl (unknown origin) assessed as inhibition constant	ki	0.0001	uM
4-chloro-3-[5-methyl-3-[4-(3-pyrrolidin-1-ylpropyl)anilino]-1,2,4-benzotriazin-7-yl]phenol	309625: Inhibition of Abl	ki	0.0001	uM
Ponatinib	1301834: Inhibition of human wild type BCR-ABL expressed in mouse BAF3 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay	ec50	0.0001	uM
methyl 4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazine-1-carboxylate	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0002	uM
ethyl 4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazine-1-carboxylate	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0002	uM
propan-2-yl 4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazine-1-carboxylate	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0002	uM
prop-2-enyl 4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazine-1-carboxylate	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0002	uM
butyl 4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazine-1-carboxylate	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0002	uM
2-chloroethyl 4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazine-1-carboxylate	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0002	uM
2-morpholin-4-ylethyl 4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazine-1-carboxylate	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0002	uM
2-[[6-[4-[(E)-but-2-enoyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0002	uM
methyl 3-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]pyrrolidine-1-carboxylate	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0002	uM
ethyl 3-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]pyrrolidine-1-carboxylate	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0002	uM
prop-2-enyl 3-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]pyrrolidine-1-carboxylate	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0002	uM
N-(2-chloro-6-methylphenyl)-2-[[2-methyl-6-[(1-prop-2-enoylpyrrolidin-3-yl)amino]pyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0002	uM
N-(2-chloro-6-methylphenyl)-2-[[2-methyl-6-[(1-propanoylpyrrolidin-3-yl)amino]pyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0002	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-[6-[2-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-2-oxoethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]hexyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1678549: Protac binding affinity at CRBN/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0002	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-[6-[2-[2-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]ethoxy]hexyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1678553: Protac binding affinity at VHL/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0002	uM
N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[[3-[(E)-2-pyridin-2-ylethenyl]-1H-indazol-6-yl]sulfanyl]propanamide	1585049: Inhibition of inactive wild type His-tagged ABL T315I mutant (229 to 500 residues) (unknown origin) expressed in baculovirus infected sf9 cells assessed as reduction in autophosphorylation preincubated for 60 mins followed by ATP addition measured after 8 hrs by ADP-Glo assay	ic50	0.0002	uM
3-(2-imidazo[1,5-b]pyridazin-7-ylethynyl)-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	1585049: Inhibition of inactive wild type His-tagged ABL T315I mutant (229 to 500 residues) (unknown origin) expressed in baculovirus infected sf9 cells assessed as reduction in autophosphorylation preincubated for 60 mins followed by ATP addition measured after 8 hrs by ADP-Glo assay	ic50	0.0002	uM
2-morpholin-4-ylethyl 4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]pyrimidin-4-yl]piperazine-1-carboxylate	2074663: Inhibition of ABL (unknown origin) using Try-2 as substrate by FRET analysis	ic50	0.0002	uM
4-(2-amino-4-pyridinyl)-N-[(2S)-1-[4-chloro-3-(trifluoromethyl)anilino]-3-hydroxy-1-oxopropan-2-yl]benzamide	2214253: Inhibition of wild type Bcr-Abl (unknown origin) using Abltide as substrate incubated for 1 hr by luminescence based ADP-glo assay	ic50	0.0002	uM
4-(2-acetamido-4-pyridinyl)-N-[(2S)-1-[4-chloro-3-(trifluoromethyl)anilino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]benzamide	2214253: Inhibition of wild type Bcr-Abl (unknown origin) using Abltide as substrate incubated for 1 hr by luminescence based ADP-glo assay	ic50	0.0002	uM
4-[[7-(2-chloro-5-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]-N-methyl-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide	309625: Inhibition of Abl	ki	0.0003	uM
2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-N-(2-methyl-4-phenoxyphenyl)-1,3-thiazole-5-carboxamide	1801731: Kinome-Wide Inhibitor Profiling from Article 10.1021/acschembio.5b01018: “Conformation-Selective Analogues of Dasatinib Reveal Insight into Kinase Inhibitor Binding and Selectivity.”	kd	0.0003	uM
phenyl 4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazine-1-carboxylate	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0003	uM
N-(2-chloro-6-methylphenyl)-2-[[2-methyl-6-[(1-methylsulfonylpyrrolidin-3-yl)amino]pyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1802640: FRET-Based Z’-Lyte Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0003	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-[6-[2-[2-[6-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-6-oxohexoxy]ethoxy]ethoxy]hexyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1678549: Protac binding affinity at CRBN/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0003	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[2-[2-[2-[6-[4-[3-[3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxyquinolin-7-yl]oxypropyl]piperazin-1-yl]hexoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1678553: Protac binding affinity at VHL/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0003	uM
N-[3-cyclopropyl-4-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]phenyl]-3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide	1648793: Inhibition of human ABL1 assessed as residual activity using EAIYAAPFAKKK as substrate by [gamma-33P]-ATP assay	ic50	0.0003	uM
3-[(2E)-3-[6-[2-[2-[2-[4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazin-1-yl]ethoxy]ethoxy]ethylamino]-6-oxohexyl]-2-[(2E,4E)-5-[3,3-dimethyl-5-sulfo-1-(3-sulfopropyl)indol-1-ium-2-yl]penta-2,4-dienylidene]-3-methyl-5-sulfoindol-1-yl]propane-1-sulfonate	1515650: Binding affinity to ABL (unknown origin) by TR-FRET assay	ki	0.0003	uM
4-[[7-(5-chloro-2-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]-N-methyl-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide	1958839: Binding affinity to Abl (unknown origin) assessed as inhibition constant	ki	0.0003	uM
N-[(2S)-1-[4-chloro-3-(trifluoromethyl)anilino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]-4-[2-(methanesulfonamido)-4-pyridinyl]benzamide	2214253: Inhibition of wild type Bcr-Abl (unknown origin) using Abltide as substrate incubated for 1 hr by luminescence based ADP-glo assay	ic50	0.0003	uM
4-(2-chloro-5-methoxyanilino)-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinoline-3-carbonitrile	2236715: Inhibition of wild-type Bcr-Abl (unknown origin) in presence of ATP	ic50	0.0003	uM
N-[(2S)-1-[4-chloro-3-(trifluoromethyl)anilino]-3-hydroxy-1-oxopropan-2-yl]-4-[2-(methanesulfonamido)-4-pyridinyl]benzamide	2214253: Inhibition of wild type Bcr-Abl (unknown origin) using Abltide as substrate incubated for 1 hr by luminescence based ADP-glo assay	ic50	0.0003	uM
3-(6-acetamido-3-pyridinyl)-N-[(2S)-1-[4-chloro-3-(trifluoromethyl)anilino]-3-hydroxy-1-oxopropan-2-yl]benzamide	2214253: Inhibition of wild type Bcr-Abl (unknown origin) using Abltide as substrate incubated for 1 hr by luminescence based ADP-glo assay	ic50	0.0003	uM
3-(6-amino-3-pyridinyl)-N-[(2S)-1-[4-chloro-3-(trifluoromethyl)anilino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]benzamide	2214253: Inhibition of wild type Bcr-Abl (unknown origin) using Abltide as substrate incubated for 1 hr by luminescence based ADP-glo assay	ic50	0.0003	uM
5-[4-[[(2S)-1-[4-chloro-3-(trifluoromethyl)anilino]-3-hydroxy-1-oxopropan-2-yl]carbamoyl]phenyl]-N,N-diethylpyridine-3-carboxamide	2214253: Inhibition of wild type Bcr-Abl (unknown origin) using Abltide as substrate incubated for 1 hr by luminescence based ADP-glo assay	ic50	0.0003	uM
4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[5-[(4-methylpiperazin-1-yl)methyl]furan-3-yl]quinoline-3-carbonitrile	275024: Inhibitory activity against Abl kinase	ic50	0.0004	uM
4-(2,4-dichloro-5-methoxyanilino)-7-[5-[(dimethylamino)methyl]furan-3-yl]-6-methoxyquinoline-3-carbonitrile	275024: Inhibitory activity against Abl kinase	ic50	0.0004	uM

CTD chemical–gene interactions

103 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Imatinib Mesylate	decreases phosphorylation, increases reaction, decreases reaction, increases phosphorylation, increases chemical synthesis (+8 more)	12
Arsenic Trioxide	affects response to substance, affects cotreatment, decreases expression, affects binding, increases reaction (+3 more)	8
ponatinib	decreases reaction, increases phosphorylation, decreases phosphorylation, decreases activity	6
Dasatinib	affects cotreatment, decreases expression, decreases phosphorylation, decreases reaction, increases phosphorylation (+2 more)	5
Cisplatin	increases response to substance, affects cotreatment, increases phosphorylation, increases expression, decreases expression (+1 more)	4
nilotinib	affects cotreatment, decreases phosphorylation, decreases reaction, increases phosphorylation, affects binding (+2 more)	3
Bortezomib	affects cotreatment, decreases phosphorylation, decreases expression, increases reaction	3
Vorinostat	affects cotreatment, decreases expression, decreases phosphorylation, decreases activity	3
trichostatin A	decreases expression	2
Adenosine Triphosphate	increases phosphorylation, increases chemical synthesis, decreases reaction, affects cotreatment	2
Doxorubicin	affects cotreatment, increases phosphorylation, increases expression, decreases expression, affects expression (+1 more)	2
Hydrogen Peroxide	decreases reaction, affects expression, increases activity	2
FR900359	affects phosphorylation	1
asciminib	decreases reaction, increases phosphorylation	1
dicrotophos	increases expression	1
myristicin	decreases expression	1
triphenyl phosphate	affects expression	1
androstane-3,17-dione	increases expression	1
bisphenol A	affects cotreatment, affects methylation, decreases methylation	1
mangiferin	decreases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
nickel sulfide	decreases expression, increases methylation, affects cotreatment, affects expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
beta-hexachlorocyclohexane	increases methylation	1
coumarin	decreases phosphorylation	1
AICA ribonucleotide	affects binding, increases reaction, affects localization, decreases expression	1
alpha-hexachlorocyclohexane	increases methylation	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
beta-methylcholine	affects expression	1

ChEMBL screening assays

3282 unique, capped per target: 3254 binding, 16 admet, 10 functional, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001091	Binding	Inhibition of ABL expressed in baculovirus system at 4 ug/ml by ELISA	Synthesis of novel 1,4-benzoxazin-3-one derivatives as inhibitors against tyrosine kinases. — *Bioorg Med Chem*
CHEMBL1963785	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ABL1	PubChem BioAssay data set
CHEMBL4189916	ADMET	Inhibition of DNA-tagged human phosphorylated partial length ABL1 T315I mutant expressed in mammalian expression system at 100 nM by qPCR method	From Cancer to Pain Target by Automated Selectivity Inversion of a Clinical Candidate. — *J Med Chem*

Cellosaurus cell lines

6,100 cell lines: 6,072 cancer cell line, 26 induced pluripotent stem cell, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0004	K-562	Cancer cell line	Female
CVCL_0087	MC3	Cancer cell line	Female
CVCL_0091	NALM-1	Cancer cell line	Female
CVCL_0094	SD-1	Transformed cell line	Female
CVCL_0103	SUP-B15	Cancer cell line	Male
CVCL_0131	A-172	Cancer cell line	Male
CVCL_0181	BV-173	Cancer cell line	Male
CVCL_0368	K562/A02	Cancer cell line	Female
CVCL_0369	K562YO	Cancer cell line	Female
CVCL_0373	KBM-5	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 383 trials:

NCT	Phase	Status	Title
NCT01042158	Phase 4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	Phase 4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	Phase 4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	Phase 4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	Phase 4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	Phase 4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	Phase 4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	Phase 4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT00081926	Phase 4	COMPLETED	Gleevec Trial in Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia
NCT00171899	Phase 4	COMPLETED	Study Comparing Standard Dose and High-dose Imatinib Mesylate in Patients With Chronic Phase Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia (CML)
NCT00390897	Phase 4	COMPLETED	Glivec® (Imatinib Mesylate, STI571) in Monotherapy Versus Glivec®-Interferon Alpha in the Treatment of Chronic-Phase Chronic Myeloid Leukaemia
NCT00461929	Phase 4	TERMINATED	Chromosome Abnormalities in Chronic Myeloid Leukemia (CML) on Imatinib. GIST Patients on Imatinib
NCT00786812	Phase 4	COMPLETED	Study of Treatment With Nilotinib in Adult Patients With Imatinib - Resistant or - Intolerant Chronic Myeloid Leukemia in Blast Crisis, Accelerated Phase or Chronic Phase
NCT00845221	Phase 4	COMPLETED	Glivec in Pediatric Chronic Myeloid Leukemia (CML)
NCT00980018	Phase 4	COMPLETED	An Exploratory Trial to Assess the Improvement of Adverse Events in Chronic Myelogenous Leukemia Patients Treated With Imatinib When Switched to Nilotinib Treatment
NCT01131325	Phase 4	TERMINATED	Study of Nilotinib in Ph+ CML-CP Patients With Low Imatinib Trough Plasma Concentrations
NCT01206088	Phase 4	COMPLETED	Tasigna in Glivec-resistant or Intolerant Patients in CML
NCT01243489	Phase 4	COMPLETED	Compliance: Role Emerges for Success in Chronic Myelogenous Leukaemia (CML): Evaluation aND Optimisation
NCT01368523	Phase 4	COMPLETED	Study of Oral AMN107 (Nilotinib) in Adult Patients With Imatinib - Resistant or - Intolerant Chronic Myeloid Leukemia in Blast Crisis, Accelerated Phase or Chronic Phase Previously Enrolled to CAMN107A2109 Trial
NCT01578213	Phase 4	COMPLETED	Validation of Digital-PCR Analysis Through Programmed Imatinib Interruption in PCR Negative CML Patients
NCT01605981	Phase 4	WITHDRAWN	Trial Evaluating Nilotinib as Treatment for Newly Diagnosed CML Patients in Accelerated Phase.
NCT01735955	Phase 4	COMPLETED	Study to Allow Access to Nilotinib for Patients Who Are on Nilotinib Treatment in a Novartis-sponsored Study
NCT01901666	Phase 4	UNKNOWN	Assessment Of Gh-Igf-1 Axis In Children With Chronic Myelogenous Leukemia (CML) In Remission
NCT02086487	Phase 4	TERMINATED	Efficacy and Safety Assessment of NIlotinib in CML Patients With Suboptimal Response on Imatinib Therapy
NCT02204722	Phase 4	TERMINATED	A Study to Evaluate Efficacy and Safety of Glinib in Newly Diagnosed CML Patients
NCT02317159	Phase 4	UNKNOWN	Efficacy and Safety of Imatinib Mesylate as First-line Treatment for the Patients With Chronic Phase of Chronic Myeloid Leukemia
NCT02546674	Phase 4	COMPLETED	Study Assessing Deep Molecular Response in Adult Patients With CML in Chronic Phase Treated With Nilotinib Firstline.
NCT03216070	Phase 4	UNKNOWN	Low-dose Dasatinib as First-line Treatment for Chronic Myeloid Leukemia
NCT04155411	Phase 4	UNKNOWN	Dose Reduced Dasatinib (70 mg Daily) as First-line Treatment for Newly Diagnosed CML-CP
NCT04877522	Phase 4	RECRUITING	Asciminib Roll-over Study
NCT07105319	Phase 4	COMPLETED	Ropeginterferon for Treatment Free Remission
NCT00864201	Phase 3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	Phase 3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	Phase 3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	Phase 3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	Phase 3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	Phase 3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT06716606	Phase 3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	Phase 3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00152139	Phase 3	COMPLETED	Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00219739	Phase 3	COMPLETED	STI571 ProspectIve RandomIzed Trial: SPIRIT
NCT00327262	Phase 3	UNKNOWN	Comparing Imatinib Standard Dose With Imatinib High Dose Induction in Pretreated Chronic Myeloid Leukemia (CML) Patients in Chronic Phase
NCT00333840	Phase 3	COMPLETED	Safety and Efficacy of Imatinib Versus Interferon-α Plus Cytarabine in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia
NCT00412360	Phase 3	COMPLETED	Single vs Double Umbilical Cord Blood Transplants in Children With High Risk Leukemia and Myelodysplasia (BMT CTN 0501)
NCT00481247	Phase 3	COMPLETED	A Phase III Study of Dasatinib vs Imatinib in Patients With Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia
NCT00514488	Phase 3	COMPLETED	Imatinib Standard Dose (400 mg/Day) Versus Imatinib High Dose (800 mg/Day)
NCT00574873	Phase 3	COMPLETED	Compare Bosutinib To Imatinib In Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive CML
NCT00760877	Phase 3	COMPLETED	Nilotinib Versus Standard Imatinib (400/600 mg Every Day (QD)) Comparing the Kinetics of Complete Molecular Response for Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Pts With Evidence of Persistent Leukemia by Real-time Quantitative Polymerase Chain Reaction (RQ-PCR)
NCT00799461	Phase 3	COMPLETED	Internet-Based Program With or Without Telephone-Based Problem-Solving Training in Helping Long-Term Survivors of Hematopoietic Stem Cell Transplant Cope With Late Complications
NCT00802841	Phase 3	COMPLETED	Randomized Phase Lll Study of Imatinib Dose Optimization vs Nilotinib in CML Patients With Suboptimal Response to Imatinib
NCT01020175	Phase 3	COMPLETED	Peripheral Blood (PB) Versus Bone Marrow (BM) in Allogeneic Stem Cell Transplantation
NCT01126892	Phase 3	COMPLETED	A Study of Nilotinib in Adult Patients With Imatinib Resistant or - Intolerant Chronic Myeloid Leukemia in Blast Crisis, Accelerated Phase or Chronic Phase
NCT01188798	Phase 3	COMPLETED	Methotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies
NCT01231412	Phase 3	COMPLETED	Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant
NCT01254188	Phase 3	COMPLETED	Safety and Efficacy of Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia Patients
NCT01275196	Phase 3	COMPLETED	Safety and Efficacy of Nilotinib vs. Imatinib in the Treatment of Newly Diagnosed Chinese Ph+ CML-CP Patients
NCT01305200	Phase 3	COMPLETED	Supersaturated Calcium Phosphate Rinse in Preventing Oral Mucositis in Young Patients Undergoing Autologous or Donor Stem Cell Transplant
NCT01366612	Phase 3	TERMINATED	Fludarabine and Busulfan vs. Fludarabine, Busulfan and Total Body Irradiation
NCT01400074	Phase 3	UNKNOWN	Efficacy of Nilotinib Versus Imatinib in Ph+ CML in Early CP Who Have a Suboptimal Molecular Response to Imatinib
NCT01535391	Phase 3	COMPLETED	Nilotinib in PH+, BCR-, ABL+ CML Patients

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ABL1 across ~30M SureChEMBL compounds — explore on Sugi Predict.