BCR

Summary

BCR (BCR activator of RhoGEF and GTPase, HGNC:1014) is a protein-coding gene on chromosome 22q11.23, encoding Breakpoint cluster region protein (P11274). Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins.

A reciprocal translocation between chromosomes 22 and 9 produces the Philadelphia chromosome, which is often found in patients with chronic myelogenous leukemia. The chromosome 22 breakpoint for this translocation is located within the BCR gene. The translocation produces a fusion protein which is encoded by sequence from both BCR and ABL, the gene at the chromosome 9 breakpoint. Although the BCR-ABL fusion protein has been extensively studied, the function of the normal BCR gene product is not clear. The unregulated tyrosine kinase activity of BCR-ABL1 contributes to the immortality of leukaemic cells. The BCR protein has serine/threonine kinase activity and is a GTPase-activating protein for p21rac and other kinases. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 613 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 362 total — 37 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 77
• Druggable target: yes — 64 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 6 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004327

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1014
Approved symbol	BCR
Name	BCR activator of RhoGEF and GTPase
Location	22q11.23
Locus type	gene with protein product
Status	Approved
Aliases	D22S662, CML, PHL, ALL
Ensembl gene	ENSG00000186716
Ensembl biotype	protein_coding
OMIM	151410
Entrez	613

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 10 protein_coding_CDS_not_defined, 9 protein_coding, 2 retained_intron

ENST00000305877, ENST00000359540, ENST00000419722, ENST00000427791, ENST00000436990, ENST00000458056, ENST00000463770, ENST00000466076, ENST00000471452, ENST00000475025, ENST00000478978, ENST00000479188, ENST00000480973, ENST00000487679, ENST00000487968, ENST00000928586, ENST00000928587, ENST00000928588, ENST00000958107, ENST00000958108, ENST00000958109

RefSeq mRNA: 2 — MANE Select: NM_004327 NM_004327, NM_021574

CCDS: CCDS13806, CCDS13807

Canonical transcript exons

ENST00000305877 — 23 exons

Exon	Start	End
ENSE00001154392	23268408	23268515
ENSE00001616269	23283977	23284098
ENSE00001654687	23289517	23289621
ENSE00001658624	23261355	23261540
ENSE00001689593	23273081	23273133
ENSE00001753733	23315433	23318037
ENSE00001755753	23273634	23273774
ENSE00001781765	23290339	23290413
ENSE00001801315	23271532	23271592
ENSE00001897802	23180509	23182239
ENSE00003484066	23287159	23287278
ENSE00003495342	23285033	23285201
ENSE00003496602	23295024	23295155
ENSE00003500461	23314552	23314714
ENSE00003517761	23260950	23261054
ENSE00003524316	23292541	23292638
ENSE00003540236	23311697	23311836
ENSE00003561884	23253799	23253980
ENSE00003562142	23312887	23313021
ENSE00003599139	23310324	23310433
ENSE00003610811	23288097	23288172
ENSE00003648666	23309424	23309483
ENSE00003668832	23313968	23314073

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 96.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.4534 / max 316.2628, expressed in 1768 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191304	11.1144	1756
191305	2.8133	1064
191306	0.3487	183
191311	0.1525	74
191307	0.0245	8

Top tissues by expression

293 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	96.77	gold quality
caudate nucleus	UBERON:0001873	96.73	gold quality
putamen	UBERON:0001874	96.52	gold quality
adenohypophysis	UBERON:0002196	96.24	gold quality
cortical plate	UBERON:0005343	95.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.28	gold quality
sural nerve	UBERON:0015488	95.04	gold quality
lower esophagus mucosa	UBERON:0035834	94.90	gold quality
pituitary gland	UBERON:0000007	94.88	gold quality
right frontal lobe	UBERON:0002810	94.35	gold quality
prefrontal cortex	UBERON:0000451	94.31	gold quality
amygdala	UBERON:0001876	94.30	gold quality
right lobe of thyroid gland	UBERON:0001119	93.93	gold quality
cingulate cortex	UBERON:0003027	93.92	gold quality
anterior cingulate cortex	UBERON:0009835	93.84	gold quality
ganglionic eminence	UBERON:0004023	93.34	gold quality
peripheral nervous system	UBERON:0000010	93.20	gold quality
tibial nerve	UBERON:0001323	93.20	gold quality
stromal cell of endometrium	CL:0002255	92.81	gold quality
left lobe of thyroid gland	UBERON:0001120	92.78	gold quality
esophagus mucosa	UBERON:0002469	92.72	gold quality
mucosa of stomach	UBERON:0001199	92.64	gold quality
lateral globus pallidus	UBERON:0002476	92.62	gold quality
skin of leg	UBERON:0001511	92.47	gold quality
frontal cortex	UBERON:0001870	92.45	gold quality
neocortex	UBERON:0001950	92.44	gold quality
telencephalon	UBERON:0001893	92.33	gold quality
forebrain	UBERON:0001890	92.26	gold quality
metanephros cortex	UBERON:0010533	92.22	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.08	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: no

Upstream regulators (CollecTRI, top): BCL6, EBF1, EGR1, HHEX, HIF1A, IRF8, JUN, MYC, NFKB, PAX1, PAX5, RELA, RUNX1, STAT1, STAT5A, TCF3, TXK

miRNA regulators (miRDB)

106 targeting BCR, 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-4673	100.00	66.64	1490
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-5582-3P	99.86	72.48	4221

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• In the fusion of the BCR and FGFR1 genes in myeloproliferative disorder, it is likely that the dimerization properties of BCR lead to aberrant FGFR1 signaling and neoplastic transformation. (PMID:11746971)
• p38 MAPK-mediated activation of NF-kappaB by the RhoGEF domain of Bcr (PMID:12096337)
• 2 cases of e19a2-positive CML with a new in-frame BCR exon e16 deletion are reported. (PMID:12145699)
• 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)
• 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)
• analyzed the clinical significance of bcr/abl mRNA levels in patients with chronic myeloid leukemia undergoing prolonged treatment with imatinib mesylate (PMID:12734675)
• BCR-ABL is inhibited by lyp tyrosine phosphatase (PMID:12764153)
• 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)
• Bcr kinase downregulates Ras signaling by phosphorylating AF-6 and binding to its PDZ domain (PMID:12808105)
• BCR-ABL has a role in differentiation of embryonic stem cells (PMID:12821944)
• Expression of BCR/ABL and BCL-2 in myeloid progenitors leads to myeloid leukemias. (PMID:12890867)
• BCR fuses with ABL 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)
• Endoplasmic reticulum stress resulting from inhibition of p210 bcr-abl triggers apoptosis in CML; leading to Bcl-2 dowmodulation and inactivation, release of caspase 12 from the ER membranes in its active form, and Ca(2+)release from the ER pool (PMID:14654084)
• ICSBP antagonizes BCR/ABL by down-regulation of bcl-2, implicating a central role for ICSBP in the pathogenesis of chronic myelogenous leukemia (PMID:14656881)
• identified a BCR/ABL-dependent increase in expression of multiple genes involved in pre-mRNA splicing; generic changes in pre-mRNA splicing as a result of p210BCR/ABL kinase activity may contribute to CML pathogenesis (PMID:14961028)
• bcr-abl transcript can be detected in the PBLs of Philadelphia chromosome (Ph)-negative essential thrombocythemia but the level of expression is markedly less than that in CML (PMID:14966468)
• BCR-ABL1 kinase activity is linked to defective pre-B cell receptor signaling (PMID:14993251)
• identified 61 genes up-regulated by BCR/ABL1, including genes encoding transcription factors, kinases, and signal transduction molecules, as well as genes regulating cell growth, differentiation, apoptosis, and cell adhesion (PMID:15145216)
• FISH analysis of the abl and bcr genes showed the signal for bcr/abl fusion on the der(22) chromosome but not on the der(9) chromosome in Philadelpha-Negative chronic myeloid leukemia. (PMID:15481444)
• We have examined the ability of Bcr to interact with other epithelial PDZ proteins and found specific binding to both the apical PDZK1 protein and the Golgi-localized Mint3. (PMID:15494376)
• Bcr-Abl mediates protection from apoptosis downstream of mitochondrial cytochrome c release (PMID:15542838)
• MCL-1 is a BCR/ABL-dependent survival factor and interesting target in chronic myeloid leukemia. (PMID:15626746)
• Results report the solution structure of AF-6 PDZ domain and its interaction with the C-terminal peptides from Neurexin and Bcr. (PMID:15684424)
• the incidence of deletions from the der(9) in childhood acute lymphoblastic leukemia is at least as high as that reported for chronic myeloid leukemia. (PMID:15716990)
• Along with ABL, deleted in leukemia, myeloid, philadelphia-positive. (PMID:15723338)
• Bcr-Abl-induced abnormalities in glucose transport regulation have roles in chronic myeloid leukaemia (PMID:15735728)
• ability of Bcr-Abl to stimulate the expression of osteopontin (PMID:15857938)
• Sequence deletoin detected in chronic myeloid leukemia. (PMID:16079118)
• Achievement of molecular remission in BCR-ABL-positive ALL occurs also in standard chemotherapy but molecular remissions begin 2-4 months later than clinicohematological ones. (PMID:16116902)
• detected the new mutation of BCR/ABL, resulting in premature termination and loss of BCR/ABL fusion protein expression (PMID:16264277)
• Identification of the CEBPB gene as a target of translational regulation in myeloid precursor cells transformed by the BCR/ABL oncogene. (PMID:16418324)
• Expressed Bcr is able to bind the transcription factor Tcf1 to disrupt the Tcf1/beta-catenin complex. Phosphorylation of Bcr by the tyrosine kinase pp60(src) can lead to dissociation of the transcriptionally inactive Bcr/Tcf1 complex (PMID:16442529)
• Enriched CD34+ cells from patients with BCR-ABL-positve chronic myelocytic leukemia in chronic phase or blast crisis do not associate blast crisis with mutation. (PMID:16442619)
• Pattern of BCR-ABL transcript levels after allograft is variable after stem cell transplantation for chronic myeloid leukemia. (PMID:16449534)
• The ability to negate calcium-dependent apoptotic signaling is a major prosurvival mechanism in Bcr-Abl-expressing cells. (PMID:16469868)
• Adaphostin+/-bortezomib circumvent imatinib resistance due to Bcr/Abl point mutations most likely through reactive oxygen species generation. (PMID:16481037)
• The minor BCR-ABL fusion gene involving a secondary Philadelphia chromosome superimposed on inversion(3) and monosomy 7 has not previously been reported in acute myelocytic leukemia. (PMID:16490599)
• The rate of glycolysis is significantly increased in Bcr-Abl expressing cells in a PI3K-dependent manner. (PMID:16494625)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	BCR	ENSDARG00000042329
danio_rerio	bcr	ENSDARG00000079286
mus_musculus	Bcr	ENSMUSG00000009681
rattus_norvegicus	Bcr	ENSRNOG00000001304
drosophila_melanogaster	RhoGAP1A	FBGN0025836

Paralogs (1): ABR (ENSG00000159842)

Protein

Protein identifiers

Breakpoint cluster region protein — P11274 (reviewed: P11274)

Alternative names: Renal carcinoma antigen NY-REN-26

All UniProt accessions (2): P11274, H0Y554

UniProt curated annotations — full annotation on UniProt →

Function. Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form. The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form. The amino terminus contains an intrinsic kinase activity. Functions as an important negative regulator of neuronal RAC1 activity. Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity. Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation.

Subunit / interactions. Homotetramer. Interacts with PDZK1. May interact with CCPG1. Interacts with FES/FPS, ABL1, PIK3R1 and GRB2. Interacts with HCK. Interacts with SH2D5. Interacts with DLG4.

Subcellular location. Postsynaptic density. Cell projection. Dendritic spine. Axon. Synapse.

Post-translational modifications. Autophosphorylated. Phosphorylated by FES/FPS on tyrosine residues, leading to down-regulation of the BCR kinase activity. Phosphorylation at Tyr-177 by HCK is important for interaction with GRB2.

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 BCR has been found in patients with chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with ABL1. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

Domain organisation. The region involved in binding to ABL1 SH2-domain is rich in serine residues and needs to be Ser/Thr phosphorylated prior to SH2 binding. This region is essential for the activation of the ABL1 tyrosine kinase and transforming potential of the chimeric BCR-ABL oncogene. The DH domain is involved in interaction with CCPG1. The amino terminus contains an intrinsic kinase activity. The central Dbl homology (DH) domain functions as a guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form. The C-terminus is a Rho-GAP domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. The protein has a unique structure having two opposing regulatory activities toward small GTP-binding proteins.

Isoforms (2)

UniProt ID	Names	Canonical?
P11274-1	1	yes
P11274-2	2

RefSeq proteins (2): NP_004318, NP_067585 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000198	RhoGAP_dom	Domain
IPR000219	DH_dom	Domain
IPR001331	GDS_CDC24_CS	Conserved_site
IPR001849	PH_domain	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR015123	Bcr-Abl_oncoprot_oligo	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036481	Bcr-Abl_oncoprot_oligo_sf	Homologous_superfamily
IPR037769	Abr/Bcr	Family

Pfam: PF00168, PF00620, PF00621, PF09036, PF19057

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (103 total): modified residue 24, sequence variant 19, helix 15, strand 10, compositionally biased region 7, region of interest 6, mutagenesis site 6, sequence conflict 6, domain 4, site 2, chain 1, coiled-coil region 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5N7E	X-RAY DIFFRACTION	1.65
5OC7	X-RAY DIFFRACTION	1.65
1K1F	X-RAY DIFFRACTION	2.2
2AIN	SOLUTION NMR
5N6R	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11274-F1	65.61	0.23

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): 426–427 (breakpoint for translocation to form bcr-abl oncogene); 1090 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Post-translational modifications (24): 1, 122, 139, 177, 202, 215, 222, 236, 246, 356, 377, 382, 385, 459, 463, 471, 473, 488, 554, 641 …

Mutagenesis-validated functional residues (6):

Position	Phenotype
177	abolishes interaction with fes and grb2.
689–690	loss of rhoa gef activity.
1090	loss of gap activity. loss of gap activity; when associated with a-1202.
1202	loss of gap activity; when associated with a-1090.
1269–1271	abolishes interaction with pdzk1.
1271	reduces interaction with pdzk1. abolishes interaction with dlg4. no effect on synaptic localization.

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-1839117	Signaling by cytosolic FGFR1 fusion mutants
R-HSA-5655302	Signaling by FGFR1 in disease
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-1226099	Signaling by FGFR in disease
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-1839124	FGFR1 mutant receptor activation
R-HSA-194315	Signaling by Rho GTPases
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 570 (showing top): GOBP_REGULATION_OF_RESPIRATORY_BURST, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_NEGATIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GOBP_ACTIVATION_OF_GTPASE_ACTIVITY, GOBP_FOCAL_ADHESION_ASSEMBLY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP

GO Biological Process (36): negative regulation of cellular extravasation (GO:0002692), renal system process (GO:0003014), protein phosphorylation (GO:0006468), phagocytosis (GO:0006909), signal transduction (GO:0007165), small GTPase-mediated signal transduction (GO:0007264), brain development (GO:0007420), actin cytoskeleton organization (GO:0030036), keratinocyte differentiation (GO:0030216), regulation of Rho protein signal transduction (GO:0035023), inner ear morphogenesis (GO:0042472), regulation of vascular permeability (GO:0043114), neutrophil degranulation (GO:0043312), negative regulation of neutrophil degranulation (GO:0043314), focal adhesion assembly (GO:0048041), homeostasis of number of cells (GO:0048872), negative regulation of inflammatory response (GO:0050728), positive regulation of phagocytosis (GO:0050766), modulation of chemical synaptic transmission (GO:0050804), neuromuscular process controlling balance (GO:0050885), regulation of small GTPase mediated signal transduction (GO:0051056), regulation of cell cycle (GO:0051726), definitive hemopoiesis (GO:0060216), negative regulation of respiratory burst (GO:0060268), negative regulation of blood vessel remodeling (GO:0060313), intracellular protein transmembrane transport (GO:0065002), cellular response to lipopolysaccharide (GO:0071222), activation of GTPase activity (GO:0090630), macrophage migration (GO:1905517), negative regulation of macrophage migration (GO:1905522), negative regulation of reactive oxygen species metabolic process (GO:2000378), cell migration (GO:0016477), response to lipopolysaccharide (GO:0032496), intracellular signal transduction (GO:0035556), positive regulation of GTPase activity (GO:0043547), establishment of localization in cell (GO:0051649)

GO Molecular Function (10): protein serine/threonine kinase activity (GO:0004674), protein tyrosine kinase activity (GO:0004713), guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (12): cytosol (GO:0005829), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), membrane (GO:0016020), axon (GO:0030424), protein-containing complex (GO:0032991), dendritic spine (GO:0043197), extracellular exosome (GO:0070062), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
RHO GTPase cycle	7
FGFR1 mutant receptor activation	1
Signaling by FGFR in disease	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Signaling by FGFR1 in disease	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Disease	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	3
cellular anatomical structure	3
GTPase regulator activity	2
synapse	2
negative regulation of leukocyte migration	1
regulation of cellular extravasation	1
cellular extravasation	1
system process	1
phosphorylation	1
protein modification process	1
endocytosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intracellular signaling cassette	1
central nervous system development	1
animal organ development	1
head development	1
cytoskeleton organization	1
actin filament-based process	1
epidermal cell differentiation	1
skin development	1
Rho protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
ear morphogenesis	1
embryonic morphogenesis	1
inner ear development	1
vascular process in circulatory system	1
blood circulation	1
regulation of biological quality	1
neutrophil activation involved in immune response	1
neutrophil mediated immunity	1
leukocyte degranulation	1
negative regulation of myeloid leukocyte mediated immunity	1
negative regulation of leukocyte degranulation	1
neutrophil degranulation	1
regulation of neutrophil degranulation	1
negative regulation of immune response	1

Protein interactions and networks

STRING

1226 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCR	ABL1	P00519	869
BCR	MLLT3	P42568	769
BCR	RARA	P10276	759
BCR	DCAF5	Q96JK2	756
BCR	AFF1	P51825	664
BCR	EVPL	Q92817	620
BCR	SH2D5	Q6ZV89	606
BCR	GFM1	Q96RP9	577
BCR	KMT2A	Q03164	556
BCR	VPREB1	P12018	551
BCR	GRB2	P29354	549
BCR	PGD	P52209	548
BCR	MLLT1	Q03111	521
BCR	TOP2A	P11388	519
BCR	MLLT10	P55197	513

IntAct

293 interactions, top by confidence:

A	B	Type	Score
CSNK2A1	EIF3J	psi-mi:“MI:0914”(association)	0.810
GRAP2	STAMBP	psi-mi:“MI:0914”(association)	0.810
CSNK2A2	EIF3J	psi-mi:“MI:0914”(association)	0.790
BCR	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.740
GRB2	WIPF3	psi-mi:“MI:0914”(association)	0.730
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
CSNK2B	RPS6KA5	psi-mi:“MI:0914”(association)	0.660
CSNK2B	RPS6KA4	psi-mi:“MI:0914”(association)	0.640
SEC13	SEC16A	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
LRRK1	ABL1	psi-mi:“MI:0914”(association)	0.590
BCR	TNKS2	psi-mi:“MI:0407”(direct interaction)	0.590
TNKS2	BCR	psi-mi:“MI:0915”(physical association)	0.590
Sh2d5	BCR	psi-mi:“MI:0914”(association)	0.580
Sh2d5	BCR	psi-mi:“MI:0915”(physical association)	0.580
BCR	Sh2d5	psi-mi:“MI:0915”(physical association)	0.580
Dok2	Nck2	psi-mi:“MI:0914”(association)	0.560
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
NAGK	ZBTB43	psi-mi:“MI:0914”(association)	0.530
RSPH9	EIF3H	psi-mi:“MI:0914”(association)	0.530

BioGRID (339): BCR (Biochemical Activity), BCR (Biochemical Activity), BCR (Reconstituted Complex), BCR (Affinity Capture-Western), BCR (Affinity Capture-MS), BCR (Affinity Capture-MS), BCR (Affinity Capture-MS), BCR (Affinity Capture-MS), BCR (Affinity Capture-MS), BCR (Affinity Capture-MS), BCR (Affinity Capture-Western), BCR (Reconstituted Complex), BCR (Affinity Capture-MS), BCR (Proximity Label-MS), BCR (Proximity Label-MS)

ESM2 similar proteins: A0A8I3NFE2, A0FI79, A1A5B6, A4D2P6, D7PF45, F1LXF1, O15357, O60346, O75808, P11274, P49796, P52734, P53349, P59672, P70268, P78524, P98174, Q0QWG9, Q13233, Q13905, Q16825, Q3MII6, Q50H33, Q5RDA9, Q62925, Q63433, Q6NS60, Q6P549, Q6PDJ6, Q6WVG3, Q7Z5H3, Q8BL80, Q8BUP8, Q8N2R8, Q8TF61, Q8VHK2, Q8WXD9, Q924W7, Q92625, Q96CX2

Diamond homologs: A0A0G2JTR4, A1A4S6, A2AB59, A2RUV4, A4IF90, A4II46, A6QNS3, A6X8Z5, A7KAX9, A7YY57, A8WRJ2, D3ZFJ3, E7EZG2, E7F3F0, F1LXF1, O14559, O94466, P11274, P15882, P30337, P34288, P38339, P46941, P52757, P55194, P81128, P97393, Q03070, Q08DP6, Q10164, Q12979, Q13017, Q15311, Q17QN0, Q20498, Q2M1Z3, Q3TBD2, Q3UIA2, Q52LW3, Q53QZ3

SIGNOR signaling

18 interactions.

A	Effect	B	Mechanism
FES	“down-regulates activity”	BCR	phosphorylation
BCR	“down-regulates activity”	RAC1	“gtpase-activating protein”
BCR-ABL	“down-regulates activity”	BCR	phosphorylation
MYC	“up-regulates quantity by expression”	BCR	“transcriptional regulation”
LNX1	“down-regulates quantity by destabilization”	BCR	ubiquitination
BCR	“down-regulates activity”	PPARG	phosphorylation
BCR-ABL	down-regulates	BCR	phosphorylation
FES	down-regulates	BCR	phosphorylation
PTPN1	down-regulates	BCR	dephosphorylation
BCR	unknown	YWHAQ	phosphorylation
BCR	unknown	YWHAZ	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 183 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	39.9×	1e-07
Activation of BAD and translocation to mitochondria	6	38.7×	1e-06
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	34.2×	2e-06
Activation of BH3-only proteins	6	25.2×	7e-06
RHO GTPases activate PKNs	7	18.8×	7e-06
Intrinsic Pathway for Apoptosis	6	14.9×	1e-04
SARS-CoV-1-host interactions	8	11.9×	2e-05
G2/M Checkpoints	10	11.4×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	7	25.6×	9e-06
protein localization to synapse	5	24.1×	4e-04
regulation of postsynaptic membrane neurotransmitter receptor levels	7	21.8×	2e-05
receptor clustering	5	19.6×	8e-04
protein targeting	7	16.1×	9e-05
mitotic spindle organization	7	12.0×	4e-04
intracellular protein localization	9	5.9×	2e-03
Wnt signaling pathway	9	5.6×	3e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 6 cancer types — BL, CLLSLL, DLBCLNOS, LUSC, NHL, WDTC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	37
Likely pathogenic	4
Uncertain significance	224
Likely benign	37
Benign	20

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1340764	GRCh37/hg19 22q11.21-11.23(chr22:21465661-24631791)x3	Pathogenic
146012	GRCh38/hg38 22q11.22-11.23(chr22:22669543-23300977)x3	Pathogenic
146442	GRCh38/hg38 22q11.21-11.23(chr22:21454661-23414686)x1	Pathogenic
148615	GRCh38/hg38 22q11.21-11.23(chr22:21454661-24247140)x1	Pathogenic
2506549	GRCh37/hg19 22q11.22-11.23(chr22:22893189-24177119)	Pathogenic
253433	GRCh37/hg19 22q11.21-11.23(chr22:21400683-23654222)x3	Pathogenic
253499	GRCh37/hg19 22q11.22-11.23(chr22:22988879-24276233)x3	Pathogenic
2684931	GRCh37/hg19 22q11.21-11.23(chr22:21798907-23652586)x3	Pathogenic
2685674	GRCh37/hg19 22q11.21-11.23(chr22:21916217-24060551)x1	Pathogenic
3391865	GRCh37/hg19 22q11.21-11.23(chr22:21798907-24636372)x3	Pathogenic
443421	GRCh37/hg19 22q11.21-11.23(chr22:21798907-23666232)x1	Pathogenic
565032	GRCh37/hg19 22q11.21-11.23(chr22:21465661-23804835)x1	Pathogenic
565043	GRCh37/hg19 22q11.21-11.23(chr22:21465661-24653491)x1	Pathogenic
59252	GRCh38/hg38 22q11.21-11.23(chr22:21443815-24235645)x1	Pathogenic
59253	GRCh38/hg38 22q11.21-11.23(chr22:21443815-23397298)x1	Pathogenic
59264	GRCh38/hg38 22q11.21-11.23(chr22:21457690-24220231)x1	Pathogenic
59267	GRCh38/hg38 22q11.21-11.23(chr22:21562911-24307688)x1	Pathogenic
59283	GRCh38/hg38 22q11.21-11.23(chr22:21623411-23315617)x1	Pathogenic
59284	GRCh38/hg38 22q11.22-11.23(chr22:22651209-23299955)x1	Pathogenic
59285	GRCh38/hg38 22q11.22-11.23(chr22:22660238-23305976)x1	Pathogenic
59286	GRCh38/hg38 22q11.22-11.23(chr22:22686122-23315617)x1	Pathogenic
59287	GRCh38/hg38 22q11.22-11.23(chr22:22703701-23285204)x1	Pathogenic
59326	GRCh38/hg38 22q11.21-11.23(chr22:21386914-23305976)x3	Pathogenic
59327	GRCh38/hg38 22q11.21-11.23(chr22:21454661-23414686)x3	Pathogenic
685586	GRCh37/hg19 22q11.21-11.23(chr22:21465661-23810042)x1	Pathogenic
686040	GRCh37/hg19 22q11.22-11.23(chr22:22962196-23652512)x1	Pathogenic
686625	GRCh37/hg19 22q11.22-11.23(chr22:22997802-23652512)x1	Pathogenic
686993	GRCh37/hg19 22q11.22-11.23(chr22:22962196-23652512)x1	Pathogenic
687011	GRCh37/hg19 22q11.22-11.23(chr22:22962196-23652512)x1	Pathogenic
687375	GRCh37/hg19 22q11.22-11.23(chr22:22962196-23652512)x1	Pathogenic

SpliceAI

4559 predictions. Top by Δscore:

Variant	Effect	Δscore
22:23253791:A:AG	acceptor_gain	1.0000
22:23253792:C:G	acceptor_gain	1.0000
22:23253796:C:G	acceptor_gain	1.0000
22:23253796:CAGAT:C	acceptor_loss	1.0000
22:23253797:A:AG	acceptor_gain	1.0000
22:23253797:AGAT:A	acceptor_gain	1.0000
22:23253798:G:GA	acceptor_loss	1.0000
22:23253798:G:GG	acceptor_gain	1.0000
22:23253798:GAT:G	acceptor_gain	1.0000
22:23253798:GATG:G	acceptor_gain	1.0000
22:23253978:GCG:G	donor_gain	1.0000
22:23253981:G:GG	donor_gain	1.0000
22:23260949:GAGT:G	acceptor_gain	1.0000
22:23261352:CA:C	acceptor_loss	1.0000
22:23261353:A:AG	acceptor_gain	1.0000
22:23261353:AGCC:A	acceptor_loss	1.0000
22:23261354:G:GC	acceptor_gain	1.0000
22:23261354:GC:G	acceptor_gain	1.0000
22:23261354:GCC:G	acceptor_gain	1.0000
22:23261354:GCCC:G	acceptor_gain	1.0000
22:23261354:GCCCA:G	acceptor_gain	1.0000
22:23261536:AGCTG:A	donor_gain	1.0000
22:23261537:GCTG:G	donor_gain	1.0000
22:23261537:GCTGG:G	donor_gain	1.0000
22:23261538:CTG:C	donor_gain	1.0000
22:23261538:CTGG:C	donor_loss	1.0000
22:23261539:TG:T	donor_gain	1.0000
22:23261539:TGG:T	donor_loss	1.0000
22:23261540:GG:G	donor_gain	1.0000
22:23261541:G:GA	donor_loss	1.0000

AlphaMissense

8366 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:23180991:T:A	W11R	1.000
22:23180991:T:C	W11R	1.000
22:23181118:G:C	R53P	1.000
22:23181120:T:C	F54L	1.000
22:23181121:T:C	F54S	1.000
22:23181122:C:A	F54L	1.000
22:23181122:C:G	F54L	1.000
22:23181124:G:C	R55P	1.000
22:23181132:T:G	Y58D	1.000
22:23181136:T:C	L59P	1.000
22:23261038:T:C	L517P	1.000
22:23261368:T:C	L527S	1.000
22:23261520:G:C	G578R	1.000
22:23261521:G:A	G578D	1.000
22:23261530:T:C	F581S	1.000
22:23268498:T:C	F615L	1.000
22:23268499:T:C	F615S	1.000
22:23268500:T:A	F615L	1.000
22:23268500:T:G	F615L	1.000
22:23273123:T:C	L655P	1.000
22:23273129:T:C	L657P	1.000
22:23273638:T:C	L660S	1.000
22:23273641:T:C	L661P	1.000
22:23273680:T:C	L674P	1.000
22:23273692:T:C	L678P	1.000
22:23273709:T:C	F684L	1.000
22:23273711:C:A	F684L	1.000
22:23273711:C:G	F684L	1.000
22:23284062:T:C	L734P	1.000
22:23285058:T:A	W755R	1.000

dbSNP variants (sampled 300 via entrez): RS1000010122 (22:23214791 T>C), RS1000014975 (22:23220771 C>G), RS1000025625 (22:23255360 C>T), RS1000032349 (22:23227429 G>A), RS1000034492 (22:23288007 G>A,C,T), RS1000056743 (22:23255161 G>A,T), RS1000063749 (22:23182631 C>G), RS1000076365 (22:23216109 C>T), RS1000080059 (22:23231247 C>A), RS1000101985 (22:23249926 C>T), RS1000119625 (22:23283245 A>G,T), RS1000128887 (22:23221966 C>G,T), RS1000129740 (22:23215846 G>A), RS1000138036 (22:23209487 G>T), RS1000184380 (22:23236034 C>T)

Disease associations

OMIM: gene MIM:151410 | disease phenotypes: MIM:608232, MIM:162091, MIM:613523

GenCC curated gene-disease

Mondo (4): chronic myeloid leukemia (MONDO:0011996), SMARCB1-related schwannomatosis (MONDO:0024517), acute lymphoblastic leukemia (MONDO:0004967), myeloid neoplasm associated with FGFR1 rearrangement (MONDO:0013296)

Orphanet (4): Chronic myeloid leukemia (Orphanet:521), Full schwannomatosis (Orphanet:93921), Acute lymphoblastic leukemia (Orphanet:513), Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement (Orphanet:168953)

HPO phenotypes

77 total (30 of 77 shown, HPO-id order):

HPO	Term
HP:0000010	Recurrent urinary tract infections
HP:0000023	Inguinal hernia
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000307	Pointed chin
HP:0000319	Smooth philtrum
HP:0000324	Facial asymmetry
HP:0000363	Abnormal earlobe morphology
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000453	Choanal atresia
HP:0000490	Deeply set eye
HP:0000581	Blepharophimosis
HP:0000657	Oculomotor apraxia
HP:0000716	Depression
HP:0000722	Compulsive behaviors
HP:0001166	Arachnodactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001382	Joint hypermobility
HP:0001442	Typified by somatic mosaicism
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001622	Premature birth

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000175_34	Height	6.000000e-06
GCST001491_24	Immune response to smallpox vaccine (IL-6)	8.000000e-06
GCST003523_25	Coenzyme Q10 levels	2.000000e-06
GCST003831_21	Asthma	4.000000e-07
GCST009598_20	Kidney stones	4.000000e-12
GCST009599_14	Kidney stones	3.000000e-12
GCST90013421_4	Left-handedness	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0007836	coenzyme Q10 measurement
EFO:0009902	handedness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (8): CHEMBL2096618 (CHIMERIC PROTEIN), CHEMBL4296119 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296120 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296137 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523751 (PROTEIN-PROTEIN INTERACTION), CHEMBL5146 (SINGLE PROTEIN), CHEMBL6193840 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193843 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

64 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 417,515 (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
CHEMBL1421	DASATINIB ANHYDROUS	4	55,003
CHEMBL1642	IMATINIB MESYLATE	4	70,143
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL4208229	ASCIMINIB	4	882
CHEMBL5416410	DASATINIB	4	655
CHEMBL571546	TIRBANIBULIN	4	1,192
CHEMBL941	IMATINIB	4	111,611
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289494	TIVOZANIB	4	4,455
CHEMBL1289601	LENVATINIB	4	8,784
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL3348923	TOVORAFENIB	4	834
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL553	ERLOTINIB	4
CHEMBL601719	CRIZOTINIB	4
CHEMBL109480	TANESPIMYCIN	3
CHEMBL165	RESVERATROL	3
CHEMBL3545413	FLUMATINIB	3
CHEMBL4297524	RADOTINIB	3
CHEMBL1908391	MASITINIB	3
CHEMBL217092	SARACATINIB	3
CHEMBL31965	CANERTINIB	3
CHEMBL3544983	TESEVATINIB	3

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs140504	BCR		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — BCR family

Binding affinities (BindingDB)

38 measured of 69 human assays (69 total across all organisms); most potent 38 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-Methyl-N-(4-(2-morpholinoethoxy) phenyl)-3-(4-(pyridin-3-yl) pyrimidin-2-ylamino) benzamide (A26)	IC50	10 nM
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide	IC50	33 nM
4-Methyl-3-(4-(pyridin-3-yl) pyrimidin-2-ylamino)-N-(3-(trifluoro methyl) phenyl) benzamide (A2)	IC50	136 nM
4-Methyl-3-(4-(pyridin-3-yl) pyrimidin-2-ylamino)-N-(pyrimidin-2-yl) benzamide (A19)	IC50	210 nM
N-(3-bromo-5-(trifluoromethyl) phenyl)-4-methyl-3-(4-(pyridin-3-yl) pyrimidin-2-ylamino) benzamide (A9)	IC50	219 nM
N-(3,5-bis(trifluoromethyl) phenyl)-4-methyl-3-(4-(pyridin-3-yl) pyrimidin-2-ylamino) benzamide (A8)	IC50	259 nM
N-(5-chloropyridin-2-yl)-4-methyl-3-(4-(pyridin-3-yl) pyrimidin-2-yl amino) benzamide (A18)	IC50	305 nM
N-(4-bromophenyl)-4-methyl-3-(4-(pyridin-3-yl) pyrimidin-2-ylamino) benzamide (A5)	IC50	483 nM
N-(3-acetylphenyl)-4-methyl-3-(4-(pyridin-3-yl) pyrimidin-2-ylamino) benzamide (A13)	IC50	542 nM
D2190	IC50	546 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
N-(2-fluorophenyl)-4-methyl-3-(4-(pyridin-3-yl) pyrimidin-2-ylamino) benzamide (A6)	IC50	569 nM
N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]-2-pyrimidin-5-yl-3,4-dihydro-1H-isoquinoline-7-carboxamide	IC50	664 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
N-(4-methoxyphenyl)-4-methyl-3-(4-(pyridin-3-yl) pyrimidin-2-yl amino) benzamide (A4)	IC50	924 nM
N-(2, 6-dimethylphenyl)-4-methyl-3-(4-(pyridin-3-yl) pyrimidin-2-yl amino) benzamide (A12)	IC50	956 nM
N-(3-fluorophenyl)-4-methyl-3-(4-(pyridin-3-yl) pyrimidin-2-ylamino) benzamide (A7)	IC50	1070 nM
4-Methyl-3-(4-(pyridin-3-yl) pyrimidin-2-ylamino)-N-p-tolyl benzamide (A10)	IC50	1100 nM
D2217	IC50	1400 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
N-(3, 4-dichlorophenyl)-4-methyl-3-(4-(pyridin-3-yl) pyrimidin-2-yl amino) benzamide (A3)	IC50	1510 nM
D2095	IC50	2100 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
4-Methyl-3-(4-(pyridin-3-yl) pyrimidin-2-ylamino)-N- (pyridin-4-yl) benzamide (A15)	IC50	2190 nM
4-Methyl-N-(pyridin-2-yl)-3-(4-(pyridin-3-yl) pyrimidin-2-ylamino) benzamide (A17)	IC50	3580 nM
4-Methyl-3-(4-(pyridin-3-yl) pyrimidin-2-ylamino)-N-(thiazol-2-yl) benzamide (A20)	IC50	3580 nM
4-Methyl-N-(pyridin-3-yl)-3-(4-(pyridin-3-yl) pyrimidin-2-ylamino) benzamide (A16)	IC50	4020 nM
D2350	IC50	4300 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
D2568	IC50	4500 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
D2196	IC50	4800 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
N-(3-methoxyphenyl)-4-methyl-3-(4-(pyridin-3-yl) pyrimidin-2-yl amino) benzamide (A14)	IC50	5240 nM
D2103	IC50	6100 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
D2473	IC50	6700 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
D2187	IC50	7200 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
D2202	IC50	7200 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
N-(3-chloro-4-fluorophenyl)-4-methyl-3-(4-(pyridin- 3-yl)pyrimidin-2-ylamino)benzamide (A1)	IC50	9570 nM
D2474	IC50	10000 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
D2475	IC50	10000 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
D2476	IC50	10000 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
D2347	IC50	10000 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
N-(4-(3-(dimethylamino)propoxy) phenyl)-4-methyl- 3-(4-(pyridin-3-yl) pyrimidin-2-ylamino) benzamide (A21)	IC50	13200 nM
N-(4-(2-(dimethylamino)ethoxy)phenyl)-4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)benzamide (A22)	IC50	21000 nM

ChEMBL bioactivities

917 potent at pChembl≥5 of 1027 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.80	IC50	0.016	nM	DASATINIB
10.52	Ki	0.03	nM	DASATINIB
10.40	EC50	0.04	nM	CHEMBL3808884
10.40	EC50	0.04	nM	DASATINIB
10.30	EC50	0.05	nM	PONATINIB
10.22	IC50	0.06	nM	CHEMBL6159841
10.10	IC50	0.08	nM	BOSUTINIB
10.06	Kd	0.088	nM	CHEMBL4746371
9.96	Kd	0.11	nM	CHEMBL4748640
9.89	Kd	0.13	nM	CHEMBL4742867
9.89	EC50	0.13	nM	DASATINIB
9.89	EC50	0.13	nM	ASCIMINIB
9.85	IC50	0.14	nM	CHEMBL334364
9.68	Kd	0.21	nM	CHEMBL4761731
9.64	Kd	0.23	nM	CHEMBL4747034
9.64	IC50	0.231	nM	CHEMBL6146115
9.64	IC50	0.23	nM	CHEMBL128706
9.62	IC50	0.24	nM	CHEMBL6114872
9.59	Kd	0.26	nM	CHEMBL4747034
9.57	IC50	0.27	nM	CHEMBL6150452
9.57	IC50	0.27	nM	CHEMBL6134515
9.55	Kd	0.28	nM	CHEMBL4748640
9.55	Kd	0.28	nM	CHEMBL4746371
9.52	EC50	0.3	nM	PONATINIB
9.52	Kd	0.3	nM	CHEMBL4796635
9.52	IC50	0.3	nM	CHEMBL6167998
9.49	Kd	0.32	nM	CHEMBL4642168
9.48	IC50	0.33	nM	CHEMBL2178270
9.48	IC50	0.33	nM	NILOTINIB
9.48	IC50	0.33	nM	CHEMBL6148910
9.48	IC50	0.33	nM	CHEMBL6101887
9.48	IC50	0.33	nM	CHEMBL6145061
9.44	IC50	0.36	nM	CHEMBL2178277
9.44	Kd	0.36	nM	CHEMBL4761731
9.42	Kd	0.38	nM	CHEMBL4742867
9.39	IC50	0.41	nM	CHEMBL2178271
9.38	IC50	0.42	nM	CHEMBL2178276
9.38	IC50	0.42	nM	CHEMBL131725
9.36	EC50	0.44	nM	CHEMBL5423801
9.35	IC50	0.45	nM	CHEMBL2178268
9.35	IC50	0.45	nM	CHEMBL2177649
9.35	Kd	0.45	nM	ASCIMINIB
9.33	Kd	0.47	nM	CHEMBL4544893
9.31	IC50	0.49	nM	CHEMBL5208315
9.30	IC50	0.5	nM	PONATINIB
9.28	IC50	0.52	nM	CHEMBL2178269
9.28	IC50	0.52	nM	CHEMBL2177648
9.28	IC50	0.52	nM	CHEMBL2177646
9.28	IC50	0.52	nM	CHEMBL2177632
9.28	IC50	0.52	nM	CHEMBL2375971

PubChem BioAssay actives

867 with measured affinity, of 2373 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
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
methyl 5-[[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]methylamino]-1H-pyrrolo[2,3-b]pyridine-2-carboxylate	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-[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
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
Asciminib	2020214: Inhibition of wild type human BCR-ABL1 using Tyr2 peptide as substrate incubated for 1 hrs in presence of dasatinib by FRET based Z-LYTE assay	ec50	0.0001	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-(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
Nilotinib	744878: Inhibition of Bcr-Abl kinase (unknown origin) after 30 mins by HTRF assay	ic50	0.0003	uM
N-[4-[[4-(dimethylamino)piperidin-1-yl]methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0003	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
N-[4-[[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0004	uM
4-chloro-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0004	uM
4-fluoro-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0004	uM
4-methyl-N-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0004	uM
N-[4-[[(3aR,6aS)-2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0004	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-[6-[2-[2-[6-[[(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]-6-oxohexoxy]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	0.0005	uM
(2S,4S)-N-[4-chloro-3-(trifluoromethyl)phenyl]-4-[4-[6-(methanesulfonamido)-3-pyridinyl]triazol-1-yl]pyrrolidine-2-carboxamide	1860252: Inhibition of wild type Bcr-Abl (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay	ic50	0.0005	uM
N-[4-[[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0005	uM
4-methyl-3-[4-[2-(methylamino)pyrimidin-5-yl]triazol-1-yl]-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0005	uM
4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(3-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0005	uM
3-(4-imidazo[1,2-a]pyridin-3-yltriazol-1-yl)-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0005	uM
4-methyl-N-[4-[[4-(4-methylpiperazin-1-yl)piperidin-1-yl]methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0005	uM
N-[4-[3-(dimethylamino)propoxy]phenyl]-4-methoxy-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide	744878: Inhibition of Bcr-Abl kinase (unknown origin) after 30 mins by HTRF assay	ic50	0.0005	uM
6-[2-[2-[6-[4-[3-[3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxyquinolin-7-yl]oxypropyl]piperazin-1-yl]hexoxy]ethoxy]ethoxy]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]hexanamide	1678549: Protac binding affinity at CRBN/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0006	uM
(2S,4S)-N-[4-chloro-3-(trifluoromethyl)phenyl]-4-[4-[6-(cyclopropanecarbonylamino)-3-pyridinyl]triazol-1-yl]pyrrolidine-2-carboxamide	1860252: Inhibition of wild type Bcr-Abl (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay	ic50	0.0006	uM
(2S,4S)-4-[4-[2-(cyclopropanecarbonylamino)-[1,3]thiazolo[5,4-b]pyridin-5-yl]triazol-1-yl]-N-(2,4-dichlorophenyl)pyrrolidine-2-carboxamide	1860252: Inhibition of wild type Bcr-Abl (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay	ic50	0.0006	uM
4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0006	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[6-[4-[3-[3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxyquinolin-7-yl]oxypropyl]piperazin-1-yl]hexoxy]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	0.0007	uM
4-methyl-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]-N-[4-(pyrrolidin-1-ylmethyl)-3-(trifluoromethyl)phenyl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0007	uM
4-bromo-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0007	uM
4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrrolo[2,3-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0007	uM
(2S,4S)-4-[4-[3-(cyclopropanecarbonylamino)-1H-indazol-6-yl]triazol-1-yl]-N-(2,4-dichlorophenyl)pyrrolidine-2-carboxamide	1860252: Inhibition of wild type Bcr-Abl (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay	ic50	0.0008	uM
2-[[6-[4-[3-[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]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	0.0008	uM
3-[4-(2-aminopyrimidin-5-yl)triazol-1-yl]-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0008	uM
tert-butyl (2S,4S)-4-[4-(6-amino-3-pyridinyl)triazol-1-yl]-2-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl]pyrrolidine-1-carboxylate	1860252: Inhibition of wild type Bcr-Abl (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay	ic50	0.0009	uM
2-chloro-6-methyl-N’-[4-methyl-3-(2-quinolin-3-ylethynyl)benzoyl]benzohydrazide	1854108: Inhibition of wild type BCR-ABL phosphorylation in mouse BaF3 cells incubated for 4 hrs by immunoblotting analysis	ic50	0.0009	uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1424919: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0010	uM
3-[2-(4-amino-1-ethylpyrazolo[3,4-d]pyrimidin-3-yl)ethynyl]-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	1206227: Inhibition of human BCR/ABL	ic50	0.0010	uM
N-[3-[2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)ethynyl]phenyl]-3-(trifluoromethyl)benzamide	1262861: Inhibition of wild-type Bcr-Abl autophosphorylation (unknown origin) expressed in mouse BA/F3 cells for 3 hrs by Western blot analysis	ec50	0.0010	uM
4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[2-(4-methylpiperazin-1-yl)oxyethoxy]quinoline-3-carbonitrile	2021812: Inhibition of human wild type BCR-ABL1 by radiometric assay	ic50	0.0010	uM
Bosutinib	2021812: Inhibition of human wild type BCR-ABL1 by radiometric assay	ic50	0.0010	uM
3-[4-[2-(cyclopropylamino)pyrimidin-5-yl]triazol-1-yl]-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0010	uM
4-methyl-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]-N-[3-(1,2,4-triazol-1-yl)-5-(trifluoromethyl)phenyl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0010	uM
N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0010	uM
4-ethyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0010	uM
Imatinib	463630: Inhibition of wild type Bcr-Abl	ic50	0.0011	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Imatinib Mesylate	increases reaction, decreases reaction, increases chemical synthesis, increases expression, affects cotreatment (+4 more)	8
Arsenic Trioxide	decreases expression, affects binding, increases expression, increases degradation, increases reaction (+1 more)	6
Dasatinib	decreases reaction, increases phosphorylation, decreases activity, affects binding, affects cotreatment (+2 more)	5
Vorinostat	decreases expression, decreases phosphorylation, decreases activity, affects cotreatment	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
nilotinib	affects binding, decreases reaction, increases chemical synthesis, increases expression, decreases phosphorylation	2
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
Estradiol	affects expression, increases expression	2
Valproic Acid	increases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	increases methylation	1
trichostatin A	decreases expression	1
arsenite	affects binding, decreases reaction	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
coumarin	decreases phosphorylation	1
muconaldehyde	decreases expression	1
cyfluthrin	increases expression	1
arsenic disulfide	decreases activity, decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects binding, decreases reaction, increases chemical synthesis, increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
purmorphamine	affects binding, decreases expression, decreases reaction	1
clothianidin	decreases expression	1
tozasertib	affects cotreatment, decreases activity	1
abrine	decreases expression	1
NCX 4040	increases expression	1
ponatinib	decreases phosphorylation	1

ChEMBL screening assays

486 unique, capped per target: 478 binding, 6 functional, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1022417	Binding	Inhibition of Bcr/Abl phosphorylation in human K562 cells at 10 uM after 1 to 3 hrs by Western blot	Design of chimeric histone deacetylase- and tyrosine kinase-inhibitors: a series of imatinib hybrides as potent inhibitors of wild-type and mutant BCR-ABL, PDGF-Rbeta, and histone deacetylases. — J Med Chem
CHEMBL5237472	Toxicity	Inhibition of BCR-ABL (unknown origin) expressed in mouse BaF3 cells assessed as cell growth inhibition incubated for 20 mins by TR-FRET assay	Imidazo[1,2-b]pyridazine as privileged scaffold in medicinal chemistry: An extensive review. — Eur J Med Chem
CHEMBL861701	Functional	Antiproliferative activity against human K562 cell line expressing Bcr-Abl	Identification of a terphenyl derivative that blocks the cell cycle in the G0-G1 phase and induces differentiation in leukemia cells. — J Med Chem

Cellosaurus cell lines

6,100 cell lines: 6,077 cancer cell line, 19 induced pluripotent stem cell, 3 transformed cell line, 1 spontaneously immortalized 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_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
CVCL_0379	Ku812	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT02086487	PHASE4	TERMINATED	Efficacy and Safety Assessment of NIlotinib in CML Patients With Suboptimal Response on Imatinib Therapy
NCT02204722	PHASE4	TERMINATED	A Study to Evaluate Efficacy and Safety of Glinib in Newly Diagnosed CML Patients
NCT02317159	PHASE4	UNKNOWN	Efficacy and Safety of Imatinib Mesylate as First-line Treatment for the Patients With Chronic Phase of Chronic Myeloid Leukemia
NCT02546674	PHASE4	COMPLETED	Study Assessing Deep Molecular Response in Adult Patients With CML in Chronic Phase Treated With Nilotinib Firstline.
NCT03216070	PHASE4	UNKNOWN	Low-dose Dasatinib as First-line Treatment for Chronic Myeloid Leukemia
NCT04155411	PHASE4	UNKNOWN	Dose Reduced Dasatinib (70 mg Daily) as First-line Treatment for Newly Diagnosed CML-CP
NCT04877522	PHASE4	RECRUITING	Asciminib Roll-over Study
NCT07105319	PHASE4	COMPLETED	Ropeginterferon for Treatment Free Remission
NCT00152139	PHASE3	COMPLETED	Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00219739	PHASE3	COMPLETED	STI571 ProspectIve RandomIzed Trial: SPIRIT
NCT00327262	PHASE3	UNKNOWN	Comparing Imatinib Standard Dose With Imatinib High Dose Induction in Pretreated Chronic Myeloid Leukemia (CML) Patients in Chronic Phase
NCT00333840	PHASE3	COMPLETED	Safety and Efficacy of Imatinib Versus Interferon-α Plus Cytarabine in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia
NCT00412360	PHASE3	COMPLETED	Single vs Double Umbilical Cord Blood Transplants in Children With High Risk Leukemia and Myelodysplasia (BMT CTN 0501)
NCT00481247	PHASE3	COMPLETED	A Phase III Study of Dasatinib vs Imatinib in Patients With Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia
NCT00514488	PHASE3	COMPLETED	Imatinib Standard Dose (400 mg/Day) Versus Imatinib High Dose (800 mg/Day)
NCT00574873	PHASE3	COMPLETED	Compare Bosutinib To Imatinib In Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive CML
NCT00760877	PHASE3	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	PHASE3	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	PHASE3	COMPLETED	Randomized Phase Lll Study of Imatinib Dose Optimization vs Nilotinib in CML Patients With Suboptimal Response to Imatinib
NCT01020175	PHASE3	COMPLETED	Peripheral Blood (PB) Versus Bone Marrow (BM) in Allogeneic Stem Cell Transplantation
NCT01126892	PHASE3	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	PHASE3	COMPLETED	Methotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies
NCT01231412	PHASE3	COMPLETED	Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant
NCT01254188	PHASE3	COMPLETED	Safety and Efficacy of Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia Patients
NCT01275196	PHASE3	COMPLETED	Safety and Efficacy of Nilotinib vs. Imatinib in the Treatment of Newly Diagnosed Chinese Ph+ CML-CP Patients