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); 286 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): 921 total — 12 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 62
• Druggable target: yes — 122 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 287 curated variant–drug associations
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_005157

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: 6 — 6 protein_coding

ENST00000318560, ENST00000372348, ENST00000393293, ENST00000929253, ENST00000929254, ENST00000929255

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.

FANTOM5 promoters (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

292 total, 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

Single-cell (SCXA)

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

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

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)

79 targeting ABL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

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

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)

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), 1 shown:

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

UniProt features (168 total): strand 34, modified residue 34, helix 31, 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)

85 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5OAZ	X-RAY DIFFRACTION	1.03
7PVS	X-RAY DIFFRACTION	1.05
4J9C	X-RAY DIFFRACTION	1.05
4J9F	X-RAY DIFFRACTION	1.09
7PW2	X-RAY DIFFRACTION	1.1
3EG3	X-RAY DIFFRACTION	1.4
4J9E	X-RAY DIFFRACTION	1.4
5DC4	X-RAY DIFFRACTION	1.48
4J9D	X-RAY DIFFRACTION	1.5
5HU9	X-RAY DIFFRACTION	1.53
7PVQ	X-RAY DIFFRACTION	1.55
5DC9	X-RAY DIFFRACTION	1.56
4JJC	X-RAY DIFFRACTION	1.6
4JJD	X-RAY DIFFRACTION	1.6
5NP2	X-RAY DIFFRACTION	1.6
1BBZ	X-RAY DIFFRACTION	1.65
4JJB	X-RAY DIFFRACTION	1.65
7PVR	X-RAY DIFFRACTION	1.65
2HZI	X-RAY DIFFRACTION	1.7
4J9H	X-RAY DIFFRACTION	1.7
4J9B	X-RAY DIFFRACTION	1.7
2O88	X-RAY DIFFRACTION	1.75
3K2M	X-RAY DIFFRACTION	1.75
2G1T	X-RAY DIFFRACTION	1.8
3EG2	X-RAY DIFFRACTION	1.8
4J9G	X-RAY DIFFRACTION	1.8
3QRJ	X-RAY DIFFRACTION	1.82
7PVV	X-RAY DIFFRACTION	1.82
3UYO	X-RAY DIFFRACTION	1.83
3EG1	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

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

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): 363 (proton acceptor); 26–27 (breakpoint for translocation to form bcr-abl and nup214-abl1 fusion proteins)

Ligand- & substrate-binding residues (3): 248–256; 271; 316–322

Post-translational modifications (35): 2, 50, 70, 115, 128, 139, 172, 185, 215, 226, 229, 253, 257, 393, 413, 446, 559, 569, 618, 619 …

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

53 pathways

ID	Pathway
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-428890	Role of ABL in ROBO-SLIT signaling
R-HSA-525793	Myogenesis
R-HSA-5663213	RHO GTPases Activate WASPs and WAVEs
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-69231	Cyclin D associated events in G1
R-HSA-8939236	RUNX1 regulates transcription of genes involved in differentiation of HSCs
R-HSA-8940973	RUNX2 regulates osteoblast differentiation
R-HSA-9664422	FCGR3A-mediated phagocytosis
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells
R-HSA-109582	Hemostasis
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-376176	Signaling by ROBO receptors
R-HSA-422475	Axon guidance
R-HSA-453279	Mitotic G1 phase and G1/S transition
R-HSA-5663205	Infectious disease
R-HSA-5693532	DNA Double-Strand Break Repair

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 (131): mitotic cell cycle (GO:0000278), neural tube closure (GO:0001843), B-1 B cell homeostasis (GO:0001922), B cell proliferation involved in immune response (GO:0002322), transitional one stage B cell differentiation (GO:0002333), 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), epidermal growth factor receptor signaling pathway (GO:0007173), positive regulation of cytosolic calcium ion concentration (GO:0007204), integrin-mediated signaling pathway (GO:0007229), canonical NF-kappaB signal transduction (GO:0007249), associative learning (GO:0008306), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), response to xenobiotic stimulus (GO:0009410), post-embryonic development (GO:0009791), regulation of autophagy (GO:0010506), positive regulation of endothelial cell migration (GO:0010595), cerebellum morphogenesis (GO:0021587), negative regulation of cell-cell adhesion (GO:0022408), microspike assembly (GO:0030035), actin cytoskeleton organization (GO:0030036), actin filament polymerization (GO:0030041), regulation of endocytosis (GO:0030100), regulation of cell adhesion (GO:0030155), neuron differentiation (GO:0030182), BMP signaling pathway (GO:0030509), negative regulation of BMP signaling pathway (GO:0030514), 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), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-2 production (GO:0032743), regulation of actin cytoskeleton organization (GO:0032956), positive regulation of osteoblast proliferation (GO:0033690), substrate adhesion-dependent cell spreading (GO:0034446), cellular response to oxidative stress (GO:0034599)

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 (22): 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), membrane (GO:0016020), cell leading edge (GO:0031252)

Reactome top-level categories

Rollup of top-14 pathways:

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

Rollup of top GO terms by namespace:

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
primary neural tube formation	1
tube closure	1
B cell homeostasis	1
B cell activation involved in immune response	1
immune response	1
B cell proliferation	1
transitional stage B cell differentiation	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
ERBB signaling pathway	1
regulation of biological quality	1
cell surface receptor signaling pathway	1
intracellular signaling cassette	1
learning	1
DNA damage response	1
intrinsic apoptotic signaling pathway	1
response to chemical	1
multicellular organism development	1
multicellular organismal process	1
autophagy	1
regulation of catabolic process	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1

Protein interactions and networks

STRING

5920 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABL1	ABI1	Q8IZP0	978
ABL1	GRB2	P29354	973
ABL1	EVPL	Q92817	958
ABL1	CRK	P46108	954
ABL1	PIK3C3	Q8NEB9	947
ABL1	ETV6	P41212	930
ABL1	HSP90AA1	P07900	922
ABL1	HSP90AB1	P08238	910
ABL1	NUP214	P35658	906
ABL1	PRDX1	P35703	904
ABL1	TP53	P04637	875
ABL1	BECN1	Q14457	872
ABL1	BCR	P11274	869
ABL1	RIN1	Q13671	865
ABL1	CRKL	P46109	856

IntAct

438 interactions, top by confidence:

A	B	Type	Score
ABL1	YWHAG	psi-mi:“MI:0915”(physical association)	0.890
RIN1	ABL1	psi-mi:“MI:0915”(physical association)	0.790
ABL1	RIN1	psi-mi:“MI:0915”(physical association)	0.790
ABL1	RIN1	psi-mi:“MI:0217”(phosphorylation reaction)	0.790
ABL1	CRKL	psi-mi:“MI:0217”(phosphorylation reaction)	0.740
ABL1	CRK	psi-mi:“MI:0915”(physical association)	0.740
ABL1	ATM	psi-mi:“MI:0915”(physical association)	0.700
ATM	ABL1	psi-mi:“MI:0915”(physical association)	0.700
ABL1	ATM	psi-mi:“MI:0407”(direct interaction)	0.700
ATM	ABL1	psi-mi:“MI:0407”(direct interaction)	0.700
ABL1	EGFR	psi-mi:“MI:0915”(physical association)	0.690
RAPGEF1	ABL1	psi-mi:“MI:0915”(physical association)	0.660
ERCC6	ABL1	psi-mi:“MI:0407”(direct interaction)	0.660
ERCC6	ABL1	psi-mi:“MI:0915”(physical association)	0.660
ABL1	ERCC6	psi-mi:“MI:0915”(physical association)	0.660
ERCC6	ABL1	psi-mi:“MI:0217”(phosphorylation reaction)	0.660
ABL1	ERCC6	psi-mi:“MI:0217”(phosphorylation reaction)	0.660
ABL1	ERCC6	psi-mi:“MI:0403”(colocalization)	0.660
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
ABL1	SRC	psi-mi:“MI:0915”(physical association)	0.590
MAP4K1	ABL1	psi-mi:“MI:0915”(physical association)	0.570
SF3B4	ABL1	psi-mi:“MI:0915”(physical association)	0.540
ADAM10	ABL1	psi-mi:“MI:0407”(direct interaction)	0.540
ADAM10	ABL1	psi-mi:“MI:0915”(physical association)	0.540
CRK	ARHGAP42	psi-mi:“MI:0914”(association)	0.530

BioGRID (579): SPRR2A (Reconstituted Complex), ABL1 (Affinity Capture-Western), ABL1 (Reconstituted Complex), CASP9 (Biochemical Activity), YWHAG (Affinity Capture-MS), YWHAB (Affinity Capture-MS), YWHAE (Affinity Capture-MS), YWHAZ (Affinity Capture-MS), YWHAH (Affinity Capture-MS), YWHAQ (Affinity Capture-MS), YWHAG (Affinity Capture-Western), YWHAB (Affinity Capture-Western), YWHAE (Affinity Capture-Western), YWHAZ (Affinity Capture-Western), YWHAH (Affinity Capture-Western)

ESM2 similar proteins: A4IFM7, A8C984, B6D5P1, B6D5P6, E9PT87, O08815, O54988, O55092, O70551, O88831, P00519, P00520, P00521, P07313, P0C865, P13234, P20689, P42684, P46087, Q13164, Q14028, Q16566, Q2KI23, Q32MK0, Q3SYS4, Q3UH66, Q3UIZ8, Q3ULB5, Q4JIM5, Q4KMM3, Q4V8B0, Q5R8Z4, Q5RDG7, Q5TGJ6, Q63553, Q6AYH9, Q6PDI6, Q80XI3, Q8BHL3, Q8BWQ5

Diamond homologs: A0A8I3NFE2, A0FI79, A0JNB0, A1Y2K1, A6QLK6, B2RZ59, B5KFD7, D3ZGS3, D7PF45, F1RDG9, G5ECJ6, O14306, O14796, O15357, O35324, O60880, O88890, O88900, P00519, P00520, P00521, P00522, P03949, P06239, P06241, P09851, P0CE43, P10447, P17713, P20936, P29350, P29351, P32019, P34370, P39688, P42684, P42685, P42686, P50904, P53356

SIGNOR signaling

200 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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 173 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
Downstream signal transduction	9	26.8×	2e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	26.2×	3e-04
Regulation of signaling by CBL	6	23.3×	7e-05
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	20.3×	7e-04
RHOU GTPase cycle	5	10.9×	5e-03
Signaling by SCF-KIT	5	9.7×	6e-03
FCGR3A-mediated phagocytosis	6	8.8×	4e-03
EPH-ephrin mediated repulsion of cells	5	8.6×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of Rac protein signal transduction	6	24.3×	2e-04
modulation of chemical synaptic transmission	9	10.3×	2e-04
protein autophosphorylation	8	7.3×	4e-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.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	11
Uncertain significance	301
Likely benign	405
Benign	105

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
1184856	NM_005157.6(ABL1):c.1388G>A (p.Gly463Asp)	Pathogenic
12625	NM_005157.6(ABL1):c.707A>T (p.Glu236Val)	Pathogenic
12626	NM_005157.6(ABL1):c.706G>A (p.Glu236Lys)	Pathogenic
12627	NM_005157.6(ABL1):c.757T>C (p.Tyr253His)	Pathogenic
12628	NM_005157.6(ABL1):c.931T>C (p.Phe311Leu)	Pathogenic
12629	NM_005157.6(ABL1):c.1052T>C (p.Met351Thr)	Pathogenic
3063094	GRCh37/hg19 9q34.11-34.13(chr9:131815597-134209182)x1	Pathogenic
374794	NM_005157.6(ABL1):c.1009G>A (p.Ala337Thr)	Pathogenic
376084	NM_005157.6(ABL1):c.730A>G (p.Met244Val)	Pathogenic
376091	NM_005157.6(ABL1):c.764A>T (p.Glu255Val)	Pathogenic
376097	NM_005157.6(ABL1):c.1187A>G (p.His396Arg)	Pathogenic
617566	Single allele	Pathogenic
1029154	NM_005157.6(ABL1):c.2351C>T (p.Pro784Leu)	Likely pathogenic
1699204	NM_005157.6(ABL1):c.143G>C (p.Trp48Ser)	Likely pathogenic
1803095	NM_005157.6(ABL1):c.1511A>G (p.Asp504Gly)	Likely pathogenic
2441840	NM_005157.6(ABL1):c.875A>T (p.Glu292Val)	Likely pathogenic
3062320	NM_005157.6(ABL1):c.1088A>C (p.Asp363Ala)	Likely pathogenic
3340737	NM_005157.6(ABL1):c.1025A>G (p.Tyr342Cys)	Likely pathogenic
625553	GRCh37/hg19 9q34.11-34.13(chr9:131670024-134514071)	Likely pathogenic
917884	NM_005157.6(ABL1):c.689C>T (p.Pro230Leu)	Likely pathogenic
982223	NM_005157.6(ABL1):c.292G>T (p.Glu98Ter)	Likely pathogenic
983211	NM_005157.6(ABL1):c.1297G>A (p.Ala433Thr)	Likely pathogenic
987880	NM_005157.6(ABL1):c.295T>C (p.Trp99Arg)	Likely pathogenic

SpliceAI

2998 predictions. Top by Δscore:

Variant	Effect	Δscore
9:130854042:T:A	acceptor_gain	1.0000
9:130854062:A:AG	acceptor_gain	1.0000
9:130854063:G:GG	acceptor_gain	1.0000
9:130854063:GA:G	acceptor_gain	1.0000
9:130854063:GAA:G	acceptor_gain	1.0000
9:130854234:AAAGG:A	donor_loss	1.0000
9:130854235:AAG:A	donor_loss	1.0000
9:130854236:AG:A	donor_loss	1.0000
9:130854237:GG:G	donor_loss	1.0000
9:130854238:GT:G	donor_loss	1.0000
9:130854239:T:A	donor_loss	1.0000
9:130854798:CAG:C	acceptor_loss	1.0000
9:130854799:A:AG	acceptor_gain	1.0000
9:130854800:G:GG	acceptor_gain	1.0000
9:130862762:GCTCT:G	acceptor_gain	1.0000
9:130872124:T:TA	acceptor_gain	1.0000
9:130872125:GCA:G	acceptor_loss	1.0000
9:130872126:CAG:C	acceptor_loss	1.0000
9:130872126:CAGG:C	acceptor_gain	1.0000
9:130872127:A:AG	acceptor_gain	1.0000
9:130872127:AG:A	acceptor_gain	1.0000
9:130872127:AGG:A	acceptor_loss	1.0000
9:130872127:AGGA:A	acceptor_gain	1.0000
9:130872127:AGGAG:A	acceptor_gain	1.0000
9:130872128:G:A	acceptor_loss	1.0000
9:130872128:G:GA	acceptor_gain	1.0000
9:130872128:GG:G	acceptor_gain	1.0000
9:130872128:GGA:G	acceptor_gain	1.0000
9:130872128:GGAG:G	acceptor_gain	1.0000
9:130872128:GGAGG:G	acceptor_gain	1.0000

AlphaMissense

7361 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:130854126:T:A	W48R	1.000
9:130854126:T:C	W48R	1.000
9:130854128:G:C	W48C	1.000
9:130854128:G:T	W48C	1.000
9:130854180:T:C	F66L	1.000
9:130854181:T:C	F66S	1.000
9:130854182:C:A	F66L	1.000
9:130854182:C:G	F66L	1.000
9:130854184:T:A	V67D	1.000
9:130854187:C:A	A68E	1.000
9:130854190:T:C	L69P	1.000
9:130854198:T:C	F72L	1.000
9:130854199:T:C	F72S	1.000
9:130854199:T:G	F72C	1.000
9:130854200:T:A	F72L	1.000
9:130854200:T:G	F72L	1.000
9:130854223:T:C	L80P	1.000
9:130854229:T:A	I82K	1.000
9:130854229:T:G	I82R	1.000
9:130854237:G:C	G85R	1.000
9:130854810:T:C	L88P	1.000
9:130854816:T:A	V90D	1.000
9:130854842:T:A	W99R	1.000
9:130854842:T:C	W99R	1.000
9:130854843:G:C	W99S	1.000
9:130854844:G:C	W99C	1.000
9:130854844:G:T	W99C	1.000
9:130854845:T:C	C100R	1.000
9:130854852:C:A	A102D	1.000
9:130854872:G:C	G109R	1.000

dbSNP variants (sampled 300 via entrez): RS1000024829 (9:130777379 T>G), RS1000026635 (9:130781426 A>G), RS1000039818 (9:130736277 A>G), RS1000066420 (9:130862466 C>A,T), RS1000074572 (9:130867067 G>A,C), RS1000131459 (9:130745376 G>T), RS1000146628 (9:130826954 T>C), RS1000158529 (9:130828831 T>G), RS1000165699 (9:130817446 CTCCT>C), RS1000178477 (9:130770465 C>T), RS1000191781 (9:130733817 C>T), RS1000201717 (9:130733719 C>T), RS1000234863 (9:130774303 C>G,T), RS1000251890 (9:130770199 C>A), RS1000264419 (9:130730317 C>G,T)

Disease associations

OMIM: gene MIM:189980 | disease phenotypes: MIM:617602, MIM:608232, MIM:215700

GenCC curated gene-disease

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

Mondo (11): congenital heart defects and skeletal malformations syndrome (MONDO:0060532), chronic myeloid leukemia (MONDO:0011996), citrullinemia (MONDO:0015991), congenital heart disease (MONDO:0005453), lip and oral cavity carcinoma (MONDO:0023644), cleft palate (MONDO:0016064), cardiomyopathy (MONDO:0004994), T-cell acute lymphoblastic leukemia (MONDO:0004963), microcephaly (MONDO:0001149), bone development disease (MONDO:0005497), connective tissue disorder (MONDO:0003900)

Orphanet (6): Marfanoid habitus-facial dysmorphism-skeletal abnormality-heart defect syndrome (Orphanet:643503), Chronic myeloid leukemia (Orphanet:521), Citrullinemia (Orphanet:187), Cleft palate (Orphanet:2014), Rare cardiomyopathy (Orphanet:167848), Moyamoya angiopathy (Orphanet:477768)

HPO phenotypes

62 total (30 of 62 shown, 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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001651_17	Response to amphetamines	8.000000e-06
GCST005174_34	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	5.000000e-06
GCST90002388_228	Lymphocyte count	9.000000e-11
GCST90002402_74	Platelet count	7.000000e-13
GCST90002404_122	Red cell distribution width	1.000000e-10
GCST90002407_77	White blood cell count	8.000000e-12

EFO canonical traits (4, from GWAS)

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 (6)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D020159	Citrullinemia	C10.228.140.163.100.937.374; C16.320.565.100.940.374; C16.320.565.189.937.374; C18.452.132.100.937.374; C18.452.648.100.940.374; C18.452.648.189.937.374
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185
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)

Molecules with ChEMBL bioactivity

122 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 343,951 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289494	TIVOZANIB	4	4,455
CHEMBL1289601	LENVATINIB	4	8,784
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1421	DASATINIB ANHYDROUS	4	55,003
CHEMBL1642	IMATINIB MESYLATE	4	70,143
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	285
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2103743	TOFACITINIB CITRATE	4	1,672
CHEMBL2105712	AFATINIB DIMALEATE	4	3,215
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL221959	TOFACITINIB	4
CHEMBL2403108	CERITINIB	4
CHEMBL24828	VANDETANIB	4
CHEMBL255863	NILOTINIB	4
CHEMBL288441	BOSUTINIB	4
CHEMBL3301607	FILGOTINIB	4
CHEMBL3348923	TOVORAFENIB	4
CHEMBL3545311	BRIGATINIB	4
CHEMBL4208229	ASCIMINIB	4
CHEMBL477772	PAZOPANIB	4

Clinical evidence (CIViC)

Drug × variant × indication: 287 predictive associations from 435 curated evidence items; also 1 prognostic.

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 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
BCR::ABL1 Fusion AND ABL1 T315I	Axitinib	Chronic Myeloid Leukemia	Sensitivity/Response	CIViC C	EID4369 +3

+257 more predictive associations (showing top 30 by evidence level).

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs121913459	ABL1		0.00	0

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)

1232 measured of 1418 human assays (1464 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
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
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
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
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
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
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
N-[7-(5-amino-4-methyl-3-pyridinyl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.09 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[3-[3-(cyclopropanecarbonylamino)isoquinolin-7-yl]-4-methylphenyl]pyrrolidine-1-carboxamide	KI	0.09 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
2-fluoro-N-[7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl]cyclopropane-1-carboxamide	KI	0.1 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(3-methyl-2-pyridinyl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.1 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
1-[7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl]-3-methylurea	KI	0.1 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(4-methyl-1H-pyrazol-5-yl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.1 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-(6-chloro-4-methyl-3-pyridinyl)isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.1 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
[2-[[7-(4-methyl-3-pyridinyl)isoquinolin-3-yl]amino]-4-pyridinyl]methanol	KI	0.1 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[7-[2-(hydroxymethyl)-3-pyridinyl]isoquinolin-3-yl]cyclopropanecarboxamide	KI	0.1 nM	US-8623889: Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof
N-[3-[3-(cyclopropanecarbonylamino)isoquinolin-7-yl]-4-methylphenyl]-4-[(dimethylamino)methyl]benzamide	KI	0.1 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

2141 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
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
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-[[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
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
4-[[7-(2-chloro-5-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]-N-ethyl-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide	309625: Inhibition of Abl	ki	0.0004	uM
4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[5-[(4-phenylpiperazin-1-yl)methyl]furan-3-yl]quinoline-3-carbonitrile	275024: Inhibitory activity against Abl kinase	ic50	0.0004	uM
2-methylpropyl 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	0.0004	uM
N-[3-chloro-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	0.0004	uM
tert-butyl N-[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]ethyl]carbamate	1515650: Binding affinity to ABL (unknown origin) by TR-FRET assay	ki	0.0004	uM
4-(2,4-dichloro-5-methoxyanilino)-7-[5-[(4-methylpiperazin-1-yl)methyl]furan-3-yl]quinoline-3-carbonitrile	275024: Inhibitory activity against Abl kinase	ic50	0.0004	uM
2-[[6-[4-[3-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[[1-[5-[[4-[chloro(difluoro)methoxy]phenyl]carbamoyl]-3-(1H-pyrazol-5-yl)-2-pyridinyl]piperidine-4-carbonyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide	2020212: Inhibition of wild type human BCR-ABL1 using Tyr2 peptide as substrate incubated for 1 hrs by FRET based Z-LYTE assay	ec50	0.0004	uM
4-[[7-(5-chloro-2-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]-N-ethyl-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide	1958839: Binding affinity to Abl (unknown origin) assessed as inhibition constant	ki	0.0004	uM
4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[(E)-4-(4-methylpiperazin-1-yl)but-1-enyl]quinoline-3-carbonitrile	480655: Inhibition of Abl	ic50	0.0004	uM
3-(2-imidazo[1,2-a]pyrazin-3-ylethynyl)-4-methyl-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]benzamide	1356713: Inhibition of Abl1 (unknown origin) incubated for 1 hr in presence of Tyrosine-2 peptide substrate by FRET based Z’-Lyte assay	ic50	0.0004	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Imatinib Mesylate	affects binding, decreases phosphorylation, increases activity, increases expression, decreases expression (+8 more)	12
Arsenic Trioxide	affects binding, increases reaction, affects localization, decreases phosphorylation, increases expression (+3 more)	8
ponatinib	decreases activity, decreases reaction, increases phosphorylation, decreases phosphorylation	5
Dasatinib	decreases reaction, increases phosphorylation, decreases activity, affects binding, affects cotreatment (+2 more)	5
Cisplatin	affects expression, increases response to substance, affects cotreatment, increases phosphorylation, increases expression (+1 more)	4
nilotinib	affects cotreatment, decreases phosphorylation, decreases reaction, increases phosphorylation, affects binding (+2 more)	3
Bortezomib	decreases phosphorylation, decreases expression, increases reaction, affects cotreatment	3
Vorinostat	affects cotreatment, decreases expression, decreases phosphorylation, decreases activity	3
trichostatin A	decreases expression	2
Adenosine Triphosphate	increases chemical synthesis, decreases reaction, affects cotreatment, increases phosphorylation	2
Doxorubicin	affects response to substance, affects cotreatment, increases phosphorylation, increases expression, decreases expression (+1 more)	2
Hydrogen Peroxide	increases activity, decreases reaction, affects expression	2
FR900359	affects 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	affects cotreatment, affects expression, decreases expression, increases methylation	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
arsenic disulfide	decreases expression, decreases activity	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)

383 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT00081926	PHASE4	COMPLETED	Gleevec Trial in Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia
NCT00171899	PHASE4	COMPLETED	Study Comparing Standard Dose and High-dose Imatinib Mesylate in Patients With Chronic Phase Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia (CML)
NCT00390897	PHASE4	COMPLETED	Glivec® (Imatinib Mesylate, STI571) in Monotherapy Versus Glivec®-Interferon Alpha in the Treatment of Chronic-Phase Chronic Myeloid Leukaemia
NCT00461929	PHASE4	TERMINATED	Chromosome Abnormalities in Chronic Myeloid Leukemia (CML) on Imatinib. GIST Patients on Imatinib
NCT00786812	PHASE4	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	PHASE4	COMPLETED	Glivec in Pediatric Chronic Myeloid Leukemia (CML)
NCT00980018	PHASE4	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	PHASE4	TERMINATED	Study of Nilotinib in Ph+ CML-CP Patients With Low Imatinib Trough Plasma Concentrations
NCT01206088	PHASE4	COMPLETED	Tasigna in Glivec-resistant or Intolerant Patients in CML
NCT01243489	PHASE4	COMPLETED	Compliance: Role Emerges for Success in Chronic Myelogenous Leukaemia (CML): Evaluation aND Optimisation
NCT01368523	PHASE4	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	PHASE4	COMPLETED	Validation of Digital-PCR Analysis Through Programmed Imatinib Interruption in PCR Negative CML Patients
NCT01605981	PHASE4	WITHDRAWN	Trial Evaluating Nilotinib as Treatment for Newly Diagnosed CML Patients in Accelerated Phase.
NCT01735955	PHASE4	COMPLETED	Study to Allow Access to Nilotinib for Patients Who Are on Nilotinib Treatment in a Novartis-sponsored Study
NCT01901666	PHASE4	UNKNOWN	Assessment Of Gh-Igf-1 Axis In Children With Chronic Myelogenous Leukemia (CML) In Remission
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