CSK

Summary

CSK (C-terminal Src kinase, HGNC:2444) is a protein-coding gene on chromosome 15q24.1, encoding Tyrosine-protein kinase CSK (P41240). Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response.

The protein encoded by this gene is involved in multiple pathways, including the regulation of Src family kinases. It plays an important role in T-cell activation through its association with the protein encoded by the protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene. This protein also phosphorylates C-terminal tyrosine residues on multiple substrates, including the protein encoded by the SRC proto-oncogene, non-receptor tyrosine kinase gene. Phosphorylation suppresses the kinase activity of the Src family tyrosine kinases. An intronic polymorphism (rs34933034) in this gene has been found to affect B-cell activation and is associated with systemic lupus erythematosus (SLE). Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1445 — RefSeq curated summary.

At a glance

• GWAS associations: 35
• Clinical variants (ClinVar): 49 total
• Druggable target: yes — 34 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004383

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2444
Approved symbol	CSK
Name	C-terminal Src kinase
Location	15q24.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000103653
Ensembl biotype	protein_coding
OMIM	124095
Entrez	1445

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 15 protein_coding, 8 retained_intron

ENST00000220003, ENST00000439220, ENST00000562066, ENST00000563010, ENST00000563894, ENST00000564216, ENST00000566464, ENST00000567123, ENST00000567135, ENST00000567571, ENST00000568329, ENST00000569321, ENST00000569462, ENST00000569915, ENST00000858351, ENST00000858352, ENST00000858353, ENST00000858354, ENST00000858355, ENST00000858356, ENST00000858357, ENST00000931146, ENST00000951979

RefSeq mRNA: 13 — MANE Select: NM_004383 NM_001127190, NM_001354988, NM_001387089, NM_001387090, NM_001387091, NM_001387092, NM_001387093, NM_001387094, NM_001387095, NM_001387096, NM_001387097, NM_001387098, NM_004383

CCDS: CCDS10269

Canonical transcript exons

ENST00000220003 — 13 exons

Exon	Start	End
ENSE00001357265	74798233	74798312
ENSE00001357268	74782080	74782720
ENSE00001870511	74802331	74803197
ENSE00003462348	74800412	74800505
ENSE00003494726	74800681	74800746
ENSE00003496772	74798826	74798938
ENSE00003521754	74798615	74798728
ENSE00003525131	74799272	74799491
ENSE00003538400	74801012	74801102
ENSE00003547997	74801522	74801595
ENSE00003579278	74801695	74801890
ENSE00003611185	74800823	74800922
ENSE00003650118	74801997	74802083

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 99.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 98.0687 / max 796.5386, expressed in 1824 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147720	79.5487	1822
147719	6.2419	1740
147724	5.6322	1230
147723	3.5474	1067
147725	1.2542	330
147721	0.4516	232
147726	0.4013	227
147729	0.3708	195
147722	0.3555	172
207588	0.1331	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.09	gold quality
monocyte	CL:0000576	98.61	gold quality
leukocyte	CL:0000738	98.55	gold quality
mononuclear cell	CL:0000842	98.53	gold quality
lower esophagus mucosa	UBERON:0035834	98.01	gold quality
spleen	UBERON:0002106	97.81	gold quality
blood	UBERON:0000178	97.79	gold quality
lymph node	UBERON:0000029	97.64	gold quality
vermiform appendix	UBERON:0001154	97.44	gold quality
esophagus mucosa	UBERON:0002469	96.55	gold quality
caecum	UBERON:0001153	96.05	gold quality
mucosa of transverse colon	UBERON:0004991	95.94	gold quality
cortical plate	UBERON:0005343	95.87	gold quality
tonsil	UBERON:0002372	94.59	gold quality
bone marrow cell	CL:0002092	94.56	gold quality
stromal cell of endometrium	CL:0002255	94.39	gold quality
gingival epithelium	UBERON:0001949	93.87	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.77	gold quality
pancreatic ductal cell	CL:0002079	93.39	silver quality
apex of heart	UBERON:0002098	93.24	gold quality
ileal mucosa	UBERON:0000331	93.13	gold quality
right lobe of liver	UBERON:0001114	93.12	gold quality
ganglionic eminence	UBERON:0004023	92.86	gold quality
small intestine	UBERON:0002108	92.77	gold quality
upper lobe of left lung	UBERON:0008952	92.74	gold quality
vagina	UBERON:0000996	92.54	gold quality
pharyngeal mucosa	UBERON:0000355	92.48	gold quality
upper lobe of lung	UBERON:0008948	92.48	gold quality
skin of leg	UBERON:0001511	92.47	gold quality
transverse colon	UBERON:0001157	92.31	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	18.99
E-CURD-112	no	2.52
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting CSK, 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-5692A	100.00	74.40	6850
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-371A-5P	99.08	66.51	1914

Literature-anchored findings (GeneRIF, showing 40)

• NMR and site-directed mutagenesis reveal novel mechanism of enzyme regulation (PMID:11724538)
• in Caco-2 cells oxidative stress-induced disruption of tight junction is mediated by the activation of c-Src. (PMID:12547828)
• cAMP regulates Csk via both spatial and enzymatic mechanisms, thereby inhibiting signaling through the T-cell receptor (PMID:12665526)
• functions of the activation loop in phosphorylation of its physiological substrate Src probed by extensive site-specific mutagenesis and kinetic studies (PMID:12686554)
• c-Src has been identified as the tyrosine kinase involved in TNF-alpha-inducing NF-kappa B transcriptional activation in the in vitro induction of COX-2 promoter activity. (PMID:12707358)
• Csk Phe183 stabilizes the movement of the alphaC-helix of the protein tyrosine kinase (PMID:12782282)
• c-Src may act as a global regulator of early proinflammatory host responses to group D adenovirus Ad19 infection of the human cornea, such as early IL-8 gene transcription. (PMID:12794155)
• Upon platelet interaction with fibrinogen, cholesterol accumulated at the tips of filopodia and at the leading edge of spreading cells; cholesterol-rich raft aggregation was accompanied by concentration of c-Src and CD63 in these cell domains (PMID:12871315)
• activation of Csk and GSK-3beta by Galphaq may contribute to the physiological and pathological effects of Gq-coupled receptors (PMID:14561750)
• model of substrate-docking site which provides the structural basis of substrate specificity in Csk (PMID:14657361)
• identification between c-Src and diacylglycerol kinase-zeta (PMID:14707140)
• C-terminal Src kinase is regulated by the leukocyte inhibitory receptor CD85j (PMID:15474475)
• Csk achieves a low K(m) for the substrate Src, not by stabilizing protein-protein interactions but rather by facilitating a fast phosphoryl transfer step (PMID:15623523)
• Csk tyrosine kinase interacts with G3BP, a new player in T-cell-antigen receptor signaling, which reduces the amount of Csk in the immune synapse. (PMID:15743820)
• c-Src plays a critical role in IL-1-induced NF-kappa B activation through the IKK complex. (PMID:15749833)
• striking functional differences between the Csk and Chk SH2 domains (PMID:15890649)
• Csk suppression is an important early event in colorectal cancer pathogenesis. (PMID:15961079)
• The SH2 domain moves in a cantilever fashion with respect to the small lobe of the kinase domain, ordering the active site for catalysis. Binding of a small Cbp-derived peptide to the SH2 domain of Csk modifies these motions, enhancing Src recognition. (PMID:16002086)
• this study reveals a mechanism by which Src family kinases may control PDGF-mediated responses both at transcriptional and translational levels. (PMID:16135530)
• analysis of docking-based substrate recognition by the catalytic domain of Csk (PMID:16439366)
• c-Src is a novel localization and binding partner for histone deacetylase (HDAC) 3 and is implicated in HDAC3 regulation. (PMID:16532030)
• Study shows EGF-stimulation-induced Csk-binding protein (Cbp) tyrosine phosphorylation followed by Cbp-Csk association, in a SFK-dependent manner.[Csk-binding protein] (PMID:16636672)
• c-Src tyrosine kinase is activated by dsRNA in human monocyte-derived dendritic cells, is recruited to TLR3 in a double-stranded (ds)RNA-dependent manner, and plays a central role in antiviral immunity. (PMID:16858407)
• beta3 integrin alters TGF-beta signaling in mammary epithelial cells via Src-mediated TbetaR-II tyrosine phosphorylation, which significantly enhanced the ability of TGF-beta to induce epithelial to mesenchymal transition and invasion. (PMID:16859511)
• EG-1 may be involved in signaling pathways including c-Src activation. (PMID:16964398)
• These data implicate an important role of c-Src in phosphorylating RelA/p65 to promote the transcriptional activity of NF-kappaB and thereby ICAM-1 expression in endothelial cells. (PMID:17012367)
• steps involving Src association, phosphorylation, and product release are fast, and a structural change in Csk participates in limiting the catalytic cycle (PMID:17018524)
• These results suggest that dimerization of Src plays an important role in the regulation of Src tyrosine kinase activity. (PMID:17056000)
• High c-Src activityis associated with ductal carcinoma in situ with high risk of recurrence or progression to invasive breast cancer. (PMID:17060931)
• in more advanced stages of colorectal carcinogenesis, increases in c-Src levels and activity are likely to have functions other than the direct promotion of tumor growth (PMID:17132222)
• The data indicate that reversible cross-linking of two cysteine residues in the SH2 domain greatly impacts catalytic function and interdomain communication in Csk. (PMID:17137590)
• these observations support the hypothesis that there is a specific coordination between the activation of the cytosolic Ah receptor and the c-Src- and cdc37-containing HSP90 complex. (PMID:17223712)
• study elucidated a nongenomic extranuclear signal mediated by the RAR-SRC interaction that is negatively regulated by CSK and is required for RA-induced neuronal differentiation (PMID:17325034)
• These data demonstrate that LPXN forms a signaling complex with Pyk2, c-Src, and PTP-PEST to regulate migration of prostate cancer cells. (PMID:17329398)
• c-Src is recruited by AF-6 to cell-cell contact sites, suggesting that c-Src is regulated by a PDZ protein in special cellular locations. (PMID:17491594)
• Csk is activated by increase of p140Cap which leads to inhibition of Src and downstream signalling as well as of cell motility and invasion (PMID:17525734)
• These results demonstrate that the chimeric strategy is useful for detailed dissection of the mechanistic basis of substrate specificity and regulation of protein tyrosine kinases. (PMID:17691821)
• Thus, these results suggest that endogenous c-Src, c-Yes, and Lyn are differentially activated through Cdc2 activation during M phase. (PMID:17692281)
• The interaction of c-Src with LNX1 depends on the C-terminal PDZ ligand of c-Src. (PMID:17936276)
• A full-length encoding cDNA of the tyrosine kinase csk gene of human lymphocytes was cloned. (PMID:17936985)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	csk	ENSDARG00000067996
mus_musculus	Csk	ENSMUSG00000032312
rattus_norvegicus	Csk	ENSRNOG00000019374

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), JAK2 (ENSG00000096968), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), 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 CSK — P41240 (reviewed: P41240)

Alternative names: C-Src kinase, Protein-tyrosine kinase CYL

All UniProt accessions (5): B2R6Q4, P41240, H3BN15, H3BU69, H3BUM9

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response. Phosphorylates tyrosine residues located in the C-terminal tails of Src-family kinases (SFKs) including LCK, SRC, HCK, FYN, LYN, CSK or YES1. Upon tail phosphorylation, Src-family members engage in intramolecular interactions between the phosphotyrosine tail and the SH2 domain that result in an inactive conformation. To inhibit SFKs, CSK is recruited to the plasma membrane via binding to transmembrane proteins or adapter proteins located near the plasma membrane. Suppresses signaling by various surface receptors, including T-cell receptor (TCR) and B-cell receptor (BCR) by phosphorylating and maintaining inactive several positive effectors such as FYN or LCK. May act as a negative regulator of EGFR and STAT3 signaling pathways.

Subunit / interactions. Homodimer (via SH3-domain). Interacts with PTPN22. Interacts with phosphorylated SIT1, PAG1, LIME1 and TGFB1I1; these interactions serve to recruit CSK to the membrane where it can phosphorylate and inhibit Src-family kinases. Interacts with SRCIN1. Interacts with RHOH. Interacts (via SH2 domain) with SCIMP; this interaction is dependent on phosphorylation of SCIMP ‘Tyr-107’. Interacts (via SH2 domain) with PRAG1 (when phosphorylated at ‘Tyr-391’); this interaction prevents translocation of CSK from the cytoplasm to the membrane leading to increased activity of CSK. Interacts with LRRK1.

Subcellular location. Cytoplasm. Cell membrane.

Tissue specificity. Expressed in lung and macrophages.

Post-translational modifications. Phosphorylated at Ser-364 by PKA, leading to increased activity. Autophosphorylated.

Domain organisation. The architecture of this protein is similar to that of Src-family kinases (SFKs) with one N-terminal SH3 domain, one SH2 domain, and a C-terminal kinase domain.

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

RefSeq proteins (13): NP_001120662, NP_001341917, NP_001374018, NP_001374019, NP_001374020, NP_001374021, NP_001374022, NP_001374023, NP_001374024, NP_001374025, NP_001374026, NP_001374027, NP_004374* (*=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
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR035027	Csk-like_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

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 (59 total): strand 20, helix 16, modified residue 5, sequence variant 4, mutagenesis site 3, domain 3, turn 2, binding site 2, initiator methionine 1, chain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3EAZ	X-RAY DIFFRACTION	1.31
3EAC	X-RAY DIFFRACTION	1.37
1BYG	X-RAY DIFFRACTION	2.4
1CSK	X-RAY DIFFRACTION	2.5
3D7T	X-RAY DIFFRACTION	2.9
3D7U	X-RAY DIFFRACTION	4.11

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41240-F1	91.57	0.75

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 (1): 314 (proton acceptor)

Ligand- & substrate-binding residues (2): 201–209; 222

Post-translational modifications (5): 184, 304, 364, 416, 2

Mutagenesis-validated functional residues (3):

Position	Phenotype
184	abolishes phosphorylation.
304	decreases activity by two-thirds and alters conformation.
364	strong decrease of phosphorylation by prkaca (catalytic subunit of pka).

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-180292	GAB1 signalosome
R-HSA-202427	Phosphorylation of CD3 and TCR zeta chains
R-HSA-354192	Integrin signaling
R-HSA-389948	Co-inhibition by PD-1
R-HSA-5674135	MAP2K and MAPK activation
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948	Signaling by high-kinase activity BRAF mutants
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-9013407	RHOH GTPase cycle
R-HSA-9649948	Signaling downstream of RAS mutants
R-HSA-9656223	Signaling by RAF1 mutants
R-HSA-9706369	Negative regulation of FLT3

MSigDB gene sets: 403 (showing top): PID_BCR_5PATHWAY, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, HORIUCHI_WTAP_TARGETS_DN, REACTOME_GAB1_SIGNALOSOME, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_PLATELET_AGGREGATION_PLUG_FORMATION, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, MORF_SNRP70, MORF_UBE2I

GO Biological Process (21): adaptive immune response (GO:0002250), protein phosphorylation (GO:0006468), negative regulation of cell population proliferation (GO:0008285), negative regulation of low-density lipoprotein particle clearance (GO:0010989), T cell costimulation (GO:0031295), negative regulation of interleukin-6 production (GO:0032715), adherens junction organization (GO:0034332), intracellular signal transduction (GO:0035556), negative regulation of Golgi to plasma membrane protein transport (GO:0042997), negative regulation of bone resorption (GO:0045779), oligodendrocyte differentiation (GO:0048709), negative regulation of phagocytosis (GO:0050765), T cell receptor signaling pathway (GO:0050852), negative regulation of T cell receptor signaling pathway (GO:0050860), negative regulation of T cell activation (GO:0050868), regulation of Fc receptor mediated stimulatory signaling pathway (GO:0060368), negative regulation of ERK1 and ERK2 cascade (GO:0070373), cellular response to peptide hormone stimulus (GO:0071375), immune system process (GO:0002376), regulation of immune system process (GO:0002682), regulation of multicellular organismal process (GO:0051239)

GO Molecular Function (14): protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), protein phosphatase binding (GO:0019903), protein kinase A catalytic subunit binding (GO:0034236), identical protein binding (GO:0042802), metal ion binding (GO:0046872), proline-rich region binding (GO:0070064), protein tyrosine kinase binding (GO:1990782), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Oncogenic MAPK signaling	5
Signaling by EGFR	1
TCR signaling	1
Signal Transduction	1
Platelet Aggregation (Plug Formation)	1
Regulation of T cell activation by CD28 family	1
RAF/MAP kinase cascade	1
RHO GTPase cycle	1
Signaling by RAS mutants	1
FLT3 Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular anatomical structure	2
protein kinase binding	2
protein binding	2
immune response	1
phosphorylation	1
protein modification process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
negative regulation of lipoprotein particle clearance	1
regulation of low-density lipoprotein particle clearance	1
low-density lipoprotein particle clearance	1
lymphocyte costimulation	1
positive regulation of T cell activation	1
negative regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
cell-cell junction organization	1
signal transduction	1
regulation of Golgi to plasma membrane protein transport	1
Golgi to plasma membrane protein transport	1
negative regulation of protein transport	1
negative regulation of protein localization to plasma membrane	1
regulation of bone resorption	1
bone resorption	1
negative regulation of bone remodeling	1
central nervous system development	1
glial cell differentiation	1
phagocytosis	1
negative regulation of endocytosis	1
regulation of phagocytosis	1
antigen receptor-mediated signaling pathway	1
T cell receptor signaling pathway	1
regulation of T cell receptor signaling pathway	1
negative regulation of antigen receptor-mediated signaling pathway	1
T cell activation	1
regulation of T cell activation	1
negative regulation of lymphocyte activation	1
negative regulation of leukocyte cell-cell adhesion	1

Protein interactions and networks

STRING

3001 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSK	PAG1	Q9NWQ8	994
CSK	PTPN22	Q9Y2R2	930
CSK	DOK3	Q7L591	922
CSK	SRC	P12931	912
CSK	PXN	P49023	904
CSK	DOK1	Q99704	884
CSK	CRK	P46108	833
CSK	ESR1	P03372	805
CSK	BCAR1	P56945	796
CSK	LILRB1	Q8NHL6	779
CSK	PTPN12	Q05209	766
CSK	LCK	P06239	729
CSK	VCL	P18206	722
CSK	CAV1	Q03135	717
CSK	CTNNB1	P35222	714

IntAct

147 interactions, top by confidence:

A	B	Type	Score
CSK	PAG1	psi-mi:“MI:0914”(association)	0.820
CSK	SRC	psi-mi:“MI:0407”(direct interaction)	0.720
SRC	CSK	psi-mi:“MI:0407”(direct interaction)	0.720
SRC	CSK	psi-mi:“MI:0217”(phosphorylation reaction)	0.720
CSK	SRC	psi-mi:“MI:0217”(phosphorylation reaction)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CD244	SH2D1B	psi-mi:“MI:0914”(association)	0.690
EGFR	CSK	psi-mi:“MI:0915”(physical association)	0.680
CSK	EGFR	psi-mi:“MI:0915”(physical association)	0.680
CSK	cagA	psi-mi:“MI:0915”(physical association)	0.660
cagA	CSK	psi-mi:“MI:0915”(physical association)	0.660
CSK	TNS3	psi-mi:“MI:0914”(association)	0.640
CSK	FRK	psi-mi:“MI:0914”(association)	0.640
PAG1	LYN	psi-mi:“MI:0915”(physical association)	0.640
CSK	PXN	psi-mi:“MI:0915”(physical association)	0.620
CSK	PTPRC	psi-mi:“MI:0217”(phosphorylation reaction)	0.620
PTPRC	CSK	psi-mi:“MI:0217”(phosphorylation reaction)	0.620
CSK	lspA1	psi-mi:“MI:0915”(physical association)	0.590
CSK	lspA1	psi-mi:“MI:0217”(phosphorylation reaction)	0.590
CSK	IGF1R	psi-mi:“MI:0915”(physical association)	0.580
TNS2	YWHAB	psi-mi:“MI:2364”(proximity)	0.570

BioGRID (911): CSK (Two-hybrid), CSK (Affinity Capture-MS), CSK (Affinity Capture-MS), AKT2 (Co-fractionation), CLIC4 (Co-fractionation), CSK (Co-fractionation), EIF4E (Co-fractionation), ILKAP (Co-fractionation), PDCD6 (Co-fractionation), PSMD9 (Co-fractionation), PDPK1 (Two-hybrid), CSK (Proximity Label-MS), CSK (PCA), CSK (Affinity Capture-Luminescence), CSK (Affinity Capture-MS)

ESM2 similar proteins: A1Z9X0, A8WUG4, A8WXF6, F1N9Y5, G5ECJ6, G5EE56, G5EGK5, O13147, O15075, O45539, O61460, P00528, P08630, P32577, P34722, P35991, P41240, P41743, P42681, P43403, P43404, P43405, P48025, P51813, P53356, P54936, P97504, Q00655, Q06187, Q07407, Q09137, Q0VBZ0, Q11179, Q13418, Q19266, Q24145, Q3SWY2, Q45FX5, Q4H3K6, Q54RB7

Diamond homologs: A0A0K3AV08, A7J1T0, A7J1T2, A7MBB4, A8X775, D3ZG83, G5EE56, H2KZW3, O01700, O19064, O22558, O43283, O54967, O60674, P00529, P00533, P00534, P00535, P03949, P04412, P06239, P06240, P08069, P08922, P08941, P09760, P09769, P11273, P11362, P13388, P14234, P14616, P14617, P16092, P16591, P18461, P21802, P21803, P21804, P22607

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
PRKACA	“up-regulates activity”	CSK	phosphorylation
CSK	down-regulates	LYN	phosphorylation
CSK	down-regulates	SRC	phosphorylation
CSK	up-regulates	NOTCH1	binding
CSK	down-regulates	LCK	phosphorylation
CSK	“down-regulates activity”	ITCH	phosphorylation
lapatinib	“down-regulates activity”	CSK	“chemical inhibition”
CSK	up-regulates	PTPRC	phosphorylation
CSK	“up-regulates activity”	MDM2	phosphorylation
CSK	“down-regulates quantity”	EEF2	phosphorylation
IGF1R	up-regulates	CSK
CREBBP	up-regulates	CSK	binding
CSK	“up-regulates activity”	CSK	phosphorylation
CSK	“down-regulates activity”	FGR	phosphorylation
CSK	“up-regulates activity”	PECAM1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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
Regulation of KIT signaling	7	47.8×	2e-08
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	7	41.3×	3e-08
Role of LAT2/NTAL/LAB on calcium mobilization	6	41.0×	5e-07
GAB1 signalosome	5	36.0×	1e-05
Regulation of signaling by CBL	6	33.9×	2e-06
SHC1 events in ERBB2 signaling	6	32.4×	2e-06
Signaling by ERBB2	8	31.5×	3e-08
Phosphorylation of CD3 and TCR zeta chains	5	30.9×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
leukocyte migration	5	27.9×	2e-04
T cell costimulation	7	23.4×	7e-06
epidermal growth factor receptor signaling pathway	7	15.5×	1e-04
ephrin receptor signaling pathway	5	15.3×	1e-03
cell surface receptor protein tyrosine kinase signaling pathway	9	14.0×	7e-06
protein dephosphorylation	6	11.9×	1e-03
insulin receptor signaling pathway	6	11.9×	1e-03
phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	11.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1723 predictions. Top by Δscore:

Variant	Effect	Δscore
15:74782716:GAGAG:G	donor_gain	1.0000
15:74782718:GAG:G	donor_gain	1.0000
15:74782719:AGGTG:A	donor_loss	1.0000
15:74798610:TGCA:T	acceptor_loss	1.0000
15:74798611:GCAG:G	acceptor_loss	1.0000
15:74798612:CAGGC:C	acceptor_loss	1.0000
15:74798613:A:C	acceptor_loss	1.0000
15:74798614:GGCC:G	acceptor_gain	1.0000
15:74798728:GG:G	donor_loss	1.0000
15:74798729:GT:G	donor_loss	1.0000
15:74798730:T:G	donor_loss	1.0000
15:74798825:G:A	acceptor_loss	1.0000
15:74798936:GCC:G	donor_gain	1.0000
15:74798937:CC:C	donor_gain	1.0000
15:74798939:G:GG	donor_gain	1.0000
15:74799270:A:AG	acceptor_gain	1.0000
15:74799270:AGTT:A	acceptor_gain	1.0000
15:74799271:G:GG	acceptor_gain	1.0000
15:74799271:GTT:G	acceptor_gain	1.0000
15:74799271:GTTG:G	acceptor_gain	1.0000
15:74799273:T:A	acceptor_gain	1.0000
15:74799325:C:A	acceptor_gain	1.0000
15:74799456:G:GT	donor_gain	1.0000
15:74799487:TGG:T	donor_gain	1.0000
15:74799492:G:C	donor_loss	1.0000
15:74799492:G:GG	donor_gain	1.0000
15:74800503:GCA:G	donor_gain	1.0000
15:74800506:G:GG	donor_gain	1.0000
15:74800676:CACAG:C	acceptor_loss	1.0000
15:74800678:CAGGC:C	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000020 (15:74801449 G>A,T), RS1000151677 (15:74781564 C>A,T), RS1000237174 (15:74787017 G>T), RS1000344503 (15:74793263 C>A,T), RS1000384307 (15:74788984 C>A), RS1000434728 (15:74780196 T>C), RS1000456620 (15:74801229 T>G), RS1000471765 (15:74783297 G>C,T), RS1000514233 (15:74786040 T>A), RS1000566433 (15:74785618 C>T), RS1000727839 (15:74791453 C>T), RS1000800543 (15:74792985 T>C), RS1000991115 (15:74787584 T>C), RS1001042551 (15:74793786 G>C), RS1001354777 (15:74786704 G>C)

Disease associations

OMIM: gene MIM:124095 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST000394_3	Diastolic blood pressure	1.000000e-23
GCST000396_3	Diastolic blood pressure	2.000000e-10
GCST001032_3	Caffeine consumption	6.000000e-07
GCST001032_7	Caffeine consumption	5.000000e-14
GCST001236_22	Blood pressure	2.000000e-15
GCST002069_17	Systemic lupus erythematosus and Systemic sclerosis	3.000000e-08
GCST003155_18	Systemic lupus erythematosus	6.000000e-15
GCST003156_46	Systemic lupus erythematosus	6.000000e-10
GCST003273_19	Diastolic blood pressure	5.000000e-06
GCST003622_53	Systemic lupus erythematosus	9.000000e-09
GCST004748_1	Lung cancer	2.000000e-07
GCST004749_40	Lung cancer in ever smokers	6.000000e-07
GCST005523_34	Celiac disease	8.000000e-09
GCST005988_12	Serum albumin levels	5.000000e-09
GCST006169_33	Diastolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	3.000000e-13
GCST006170_36	Systolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	5.000000e-14
GCST006172_19	Mean arterial pressure x alcohol consumption (light vs heavy) interaction (2df test)	1.000000e-15
GCST006187_40	Diastolic blood pressure (cigarette smoking interaction)	8.000000e-33
GCST006187_41	Diastolic blood pressure (cigarette smoking interaction)	5.000000e-30
GCST006188_44	Systolic blood pressure (cigarette smoking interaction)	1.000000e-28
GCST006188_45	Systolic blood pressure (cigarette smoking interaction)	4.000000e-23
GCST006231_65	Mean arterial pressure	2.000000e-15
GCST006585_1699	Blood protein levels	4.000000e-10
GCST007267_147	Systolic blood pressure	1.000000e-17
GCST007400_63	Systemic lupus erythematosus	5.000000e-06
GCST007927_37	Medication use (beta blocking agents)	2.000000e-08
GCST007928_51	Medication use (diuretics)	3.000000e-15
GCST007930_64	Medication use (agents acting on the renin-angiotensin system)	9.000000e-21
GCST008363_100	Offspring birth weight	2.000000e-11
GCST008828_4	Hypertension	8.000000e-06

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0004330	coffee consumption
EFO:0006340	mean arterial pressure
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement
EFO:0009929	Beta blocking agent use measurement
EFO:0009928	Diuretic use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0006781	coffee consumption measurement
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2634 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

34 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 376,752 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL217092	SARACATINIB	3	3,982
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1738757	REBASTINIB	2	1,478
CHEMBL206834	BAFETINIB	2	1,024
CHEMBL215152	DEFOSBARASERTIB	2
CHEMBL2165191	AZD-6482	2
CHEMBL3545396	BMS-690514	2
CHEMBL475251	R-406	2
CHEMBL495727	AT-9283	2
CHEMBL572878	TOZASERTIB	2
CHEMBL575448	BMS-754807	2
CHEMBL607707	PELITINIB	2
CHEMBL1614725	TAK-285	1
CHEMBL1908397	KW-2449	1

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1378942	Efficacy	3	hydrochlorothiazide	Hypertension

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1378942	CSK	3	3.00	1	hydrochlorothiazide
rs4886410	CSK		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Csk family

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
NG-25	Inhibition	7.25	pIC50
rivoceranib	Inhibition	6.28	pIC50
PP1	Inhibition	6.28	pIC50

Binding affinities (BindingDB)

197 measured of 237 human assays (237 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
IBRUTINIB	IC50	0.8 nM	US-9278100: Inhibitors of bruton’s tyrosine kinase for the treatment of solid tumors
N-[4-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexyl]prop-2-enamide	IC50	1.1 nM	US-9278100: Inhibitors of bruton’s tyrosine kinase for the treatment of solid tumors
Staurosporine	KD	1.7 nM
N-[3-[1-cyclohexyl-4-[2-[[6-(4-methylpiperazin-1-yl)-3-pyridinyl]amino]pyrimidin-4-yl]pyrazol-3-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide	IC50	2.5 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-dichloro-N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(5-fluoro-3-pyridinyl)-1,3-thiazol-4-yl]-2-fluorophenyl]-3-methylbenzenesulfonamide	IC50	2.7 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[2-tert-butyl-5-[2-[(6-morpholin-4-yl-3-pyridinyl)amino]pyrimidin-4-yl]-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide	IC50	2.8 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-difluoro-N-[2-fluoro-3-[2-(5-fluoro-2-pyridinyl)-5-[2-[(6-methoxy-3-pyridinyl)amino]pyrimidin-4-yl]-1,3-thiazol-4-yl]phenyl]benzenesulfonamide	IC50	2.9 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-dichloro-N-[2-fluoro-3-[5-[2-(methylamino)pyrimidin-4-yl]-2-(2-methylpyrimidin-5-yl)-1,3-thiazol-4-yl]phenyl]-3-methylbenzenesulfonamide	IC50	3.6 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[2-tert-butyl-5-[2-[[6-(4-methylpiperazin-1-yl)-3-pyridinyl]amino]pyrimidin-4-yl]-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide	IC50	3.7 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[5-(2-aminopyrimidin-4-yl)-2-phenyl-1,3-thiazol-4-yl]-2-fluoro-5-methoxyphenyl]-2,6-difluorobenzenesulfonamide	IC50	4.1 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[2-(azetidin-1-yl)-5-[2-(cyclopropylamino)pyrimidin-4-yl]-1,3-thiazol-4-yl]-2-fluorophenyl]-3-chloro-2,6-difluorobenzenesulfonamide	IC50	4.1 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-dichloro-N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(2-methylpyrimidin-5-yl)-1,3-thiazol-4-yl]-2-fluorophenyl]benzenesulfonamide	IC50	4.5 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[1-cyclohexyl-4-[2-[(6-morpholin-4-yl-3-pyridinyl)amino]pyrimidin-4-yl]pyrazol-3-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide	IC50	4.6 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-dichloro-N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(2-methylpyrimidin-5-yl)-1,3-thiazol-4-yl]-2-fluorophenyl]-3-methylbenzenesulfonamide	IC50	4.8 nM	US-12427146: C-terminal SRC kinase inhibitors
3-chloro-N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-piperidin-1-yl-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide	IC50	4.9 nM	US-12427146: C-terminal SRC kinase inhibitors
3-chloro-N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-pyrrolidin-1-yl-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide	IC50	5.2 nM	US-12427146: C-terminal SRC kinase inhibitors
3-chloro-2,6-difluoro-N-[2-fluoro-3-[2-(5-fluoro-3-pyridinyl)-5-[2-(2-hydroxyethylamino)pyrimidin-4-yl]-1,3-thiazol-4-yl]phenyl]benzenesulfonamide	IC50	5.4 nM	US-12427146: C-terminal SRC kinase inhibitors
3-chloro-N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(5-fluoro-3-pyridinyl)-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide	IC50	5.6 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-dichloro-N-[2-fluoro-3-[2-(5-fluoro-3-pyridinyl)-5-[2-(methylamino)pyrimidin-4-yl]-1,3-thiazol-4-yl]phenyl]benzenesulfonamide	IC50	5.8 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-dichloro-N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(5-fluoro-3-pyridinyl)-1,3-thiazol-4-yl]-2-fluorophenyl]benzenesulfonamide	IC50	6 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-dichloro-N-[2-fluoro-3-[5-[2-(2-hydroxyethylamino)pyrimidin-4-yl]-2-(2-methylpyrimidin-5-yl)-1,3-thiazol-4-yl]phenyl]-3-methylbenzenesulfonamide	IC50	6 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-dichloro-N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-piperidin-1-yl-1,3-thiazol-4-yl]-2-fluorophenyl]-3-methylbenzenesulfonamide	IC50	6.2 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[2-(3,3-difluoropyrrolidin-1-yl)-5-[2-(methylamino)pyrimidin-4-yl]-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide	IC50	6.4 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-dichloro-N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(6-methylpyridazin-3-yl)-1,3-thiazol-4-yl]-2-fluorophenyl]-3-methylbenzenesulfonamide	IC50	6.5 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[5-(2-aminopyrimidin-4-yl)-2-(2-methylpyrimidin-5-yl)-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-dichlorobenzenesulfonamide	IC50	6.8 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-dichloro-N-[2-fluoro-3-[5-[2-(methylamino)pyrimidin-4-yl]-2-(2-methylpyrimidin-5-yl)-1,3-thiazol-4-yl]phenyl]benzenesulfonamide	IC50	6.9 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-difluoro-N-[2-fluoro-3-[5-[2-(methylamino)pyrimidin-4-yl]-2-piperidin-1-yl-1,3-thiazol-4-yl]phenyl]benzenesulfonamide	IC50	7.1 nM	US-12427146: C-terminal SRC kinase inhibitors
3-chloro-N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(dimethylamino)-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide	IC50	7.3 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[3-[2-(cyclopropylamino)pyrimidin-4-yl]-7-methoxyimidazo[1,2-a]pyridin-2-yl]-2-fluorophenyl]-2,6-difluoro-3-methylbenzenesulfonamide	IC50	7.4 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[2-(diethylamino)-5-[2-(methylamino)pyrimidin-4-yl]-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide	IC50	7.4 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-piperidin-1-yl-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide	IC50	7.4 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-dichloro-N-[2-fluoro-3-[5-[2-(2-hydroxyethylamino)pyrimidin-4-yl]-2-piperidin-1-yl-1,3-thiazol-4-yl]phenyl]-3-methylbenzenesulfonamide	IC50	7.5 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-dichloro-N-[2-fluoro-3-[2-(5-fluoro-3-pyridinyl)-5-[2-(2-hydroxyethylamino)pyrimidin-4-yl]-1,3-thiazol-4-yl]phenyl]benzenesulfonamide	IC50	7.6 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-difluoro-N-[2-fluoro-3-[5-[2-(methylamino)pyrimidin-4-yl]-2-[methyl(2,2,2-trifluoroethyl)amino]-1,3-thiazol-4-yl]phenyl]benzenesulfonamide	IC50	7.8 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-dichloro-N-[2-fluoro-3-[5-[2-(2-hydroxyethylamino)pyrimidin-4-yl]-2-(2-methylpyrimidin-5-yl)-1,3-thiazol-4-yl]phenyl]benzenesulfonamide	IC50	8.1 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-dichloro-N-[3-[2-(dimethylamino)-5-[2-(methylamino)pyrimidin-4-yl]-1,3-thiazol-4-yl]-2-fluorophenyl]-3-methylbenzenesulfonamide	IC50	8.3 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-dichloro-N-[2-fluoro-3-[2-(5-fluoro-3-pyridinyl)-5-[2-(2-hydroxyethylamino)pyrimidin-4-yl]-1,3-thiazol-4-yl]phenyl]-3-methylbenzenesulfonamide	IC50	8.5 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-difluoro-N-[2-fluoro-3-[2-(5-fluoro-3-pyridinyl)-5-[2-(methylamino)pyrimidin-4-yl]-1,3-thiazol-4-yl]phenyl]benzenesulfonamide	IC50	8.8 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(5-fluoro-3-pyridinyl)-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluoro-3-methylbenzenesulfonamide	IC50	9.1 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(2-methylpyrimidin-5-yl)-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluoro-3-methylbenzenesulfonamide	IC50	9.3 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[5-(2-aminopyrimidin-4-yl)-2-(5-fluoro-3-pyridinyl)-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-dichlorobenzenesulfonamide	IC50	9.4 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-difluoro-N-[2-fluoro-3-[5-[2-(methylamino)pyrimidin-4-yl]-2-(2,2,2-trifluoroethylamino)-1,3-thiazol-4-yl]phenyl]benzenesulfonamide	IC50	9.9 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	IC50	10 nM	US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof
2,6-difluoro-N-[2-fluoro-3-[5-[2-(methylamino)pyrimidin-4-yl]-2-piperidin-1-yl-1,3-thiazol-4-yl]phenyl]-3-methylbenzenesulfonamide	IC50	10.1 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-piperidin-1-yl-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluoro-3-methylbenzenesulfonamide	IC50	10.2 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(6-methylpyridazin-3-yl)-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluoro-3-methylbenzenesulfonamide	IC50	10.3 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[5-(2-aminopyrimidin-4-yl)-2-(2-methylpyrimidin-5-yl)-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-dichloro-3-methylbenzenesulfonamide	IC50	10.5 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[5-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(dimethylamino)-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluoro-3-methylbenzenesulfonamide	IC50	11.2 nM	US-12427146: C-terminal SRC kinase inhibitors
N-[3-[2-tert-butyl-5-[2-(cyclopropylamino)pyrimidin-4-yl]-1,3-thiazol-4-yl]-2-fluorophenyl]-3-chloro-2,6-difluorobenzenesulfonamide	IC50	11.4 nM	US-12427146: C-terminal SRC kinase inhibitors
2,6-difluoro-N-[2-fluoro-3-[2-(5-fluoro-3-pyridinyl)-5-[2-(propan-2-ylamino)pyrimidin-4-yl]-1,3-thiazol-4-yl]phenyl]benzenesulfonamide	IC50	11.8 nM	US-12427146: C-terminal SRC kinase inhibitors

ChEMBL bioactivities

172 potent at pChembl≥5 of 191 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Kd	1	nM	DASATINIB
8.89	IC50	1.3	nM	DASATINIB
8.77	IC50	1.7	nM	CHEMBL591325
8.70	IC50	2	nM	CHEMBL4582324
8.66	IC50	2.2	nM	IBRUTINIB
8.64	IC50	2.3	nM	IBRUTINIB
8.62	IC50	2.4	nM	CHEMBL3647967
8.40	IC50	4	nM	CHEMBL4537527
8.40	IC50	4	nM	CHEMBL4443654
8.40	IC50	4	nM	CHEMBL4577049
8.40	IC50	4	nM	CHEMBL4545269
8.40	IC50	4	nM	CHEMBL4445994
8.35	IC50	4.5	nM	CHEMBL589630
8.30	IC50	5	nM	CHEMBL4443654
8.22	IC50	6	nM	CHEMBL4537527
8.15	Kd	7	nM	CHEMBL3991931
8.15	IC50	7.12	nM	STAUROSPORINE
8.10	IC50	8	nM	CHEMBL4437906
8.05	IC50	9	nM	CHEMBL4798527
8.05	IC50	8.91	nM	STAUROSPORINE
7.90	IC50	12.7	nM	PONATINIB
7.90	IC50	12.5	nM	CHEMBL5705829
7.89	IC50	13	nM	CHEMBL4469360
7.84	IC50	14.3	nM	STAUROSPORINE
7.68	IC50	21	nM	CHEMBL4483095
7.66	Kd	22	nM	DASATINIB
7.60	IC50	25	nM	REBASTINIB
7.60	IC50	25	nM	CHEMBL5705842
7.60	IC50	25.1	nM	CHEMBL5705822
7.58	IC50	26	nM	CHEMBL4483095
7.55	Kd	28	nM	CHEMBL249097
7.52	Kd	30	nM	CHEMBL4462318
7.50	Kd	32	nM	BOSUTINIB
7.43	IC50	37	nM	IBRUTINIB
7.39	IC50	41	nM	CHEMBL47203
7.38	IC50	42	nM	CHEMBL4469360
7.28	IC50	52	nM	CHEMBL5832400
7.27	IC50	54	nM	CHEMBL5407103
7.25	IC50	56.4	nM	CHEMBL4125960
7.23	IC50	59	nM	CHEMBL5705835
7.22	Kd	60	nM	CHEMBL386051
7.20	IC50	63	nM	BOSUTINIB
7.16	IC50	70	nM	CHEMBL4591137
7.10	IC50	79	nM	CHEMBL4555519
7.10	IC50	80	nM	CHEMBL4518970
7.10	IC50	80	nM	CHEMBL1762530
7.09	IC50	80.9	nM	CHEMBL5705847
6.92	Kd	120	nM	FORETINIB
6.80	Kd	160	nM	R-406
6.79	IC50	162	nM	CHEMBL4106978

PubChem BioAssay actives

174 with measured affinity, of 1720 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	435904: Binding constant for full-length CSK	kd	0.0010	uM
8-[2-(dimethylamino)ethoxy]-2-(4-phenoxyphenyl)-6,11-dihydro-5H-pyrazolo[5,1-b][1,3]benzodiazepine-1-carboxamide	452197: Inhibition of Csk	ic50	0.0017	uM
1-[1-(tert-butylcarbamoyl)piperidin-4-yl]-N-[4-[(6-methoxypyrazolo[1,5-a]pyridine-3-carbonyl)amino]-3-methylphenyl]indazole-3-carboxamide	1512574: Inhibition of CSK (unknown origin) using fluorescent labeled peptide as substrate in presence of ATP at Km concentration by caliper method	ic50	0.0020	uM
Ibrutinib	1714850: Inhibition of CSK (unknown origin)	ic50	0.0023	uM
N-[3-chloro-4-[(6-methoxypyrazolo[1,5-a]pyridine-3-carbonyl)amino]phenyl]-1-[1-(3-cyano-3-methylbutanoyl)piperidin-4-yl]-5-fluoroindazole-3-carboxamide	1512569: Inhibition of His-tagged/GST-tagged CSK (unknown origin) incubated for 1 hr by TR-FRET assay	ic50	0.0030	uM
1-[1-(3-cyano-3-methylbutanoyl)piperidin-4-yl]-N-[3-methyl-4-(pyrazolo[1,5-a]pyridine-3-carbonylamino)phenyl]indazole-3-carboxamide	1512569: Inhibition of His-tagged/GST-tagged CSK (unknown origin) incubated for 1 hr by TR-FRET assay	ic50	0.0030	uM
1-[1-(tert-butylcarbamoyl)piperidin-4-yl]-N-[3-methyl-4-(pyrazolo[1,5-a]pyridine-3-carbonylamino)phenyl]indazole-3-carboxamide	1512569: Inhibition of His-tagged/GST-tagged CSK (unknown origin) incubated for 1 hr by TR-FRET assay	ic50	0.0030	uM
1-[1-(tert-butylcarbamoyl)piperidin-4-yl]-N-[3-chloro-4-(pyrazolo[1,5-a]pyridine-3-carbonylamino)phenyl]indazole-3-carboxamide	1512574: Inhibition of CSK (unknown origin) using fluorescent labeled peptide as substrate in presence of ATP at Km concentration by caliper method	ic50	0.0040	uM
1-[1-(tert-butylcarbamoyl)piperidin-4-yl]-N-[3-chloro-4-[(6-methoxypyrazolo[1,5-a]pyridine-3-carbonyl)amino]phenyl]-5-fluoroindazole-3-carboxamide	1512569: Inhibition of His-tagged/GST-tagged CSK (unknown origin) incubated for 1 hr by TR-FRET assay	ic50	0.0040	uM
4-amino-5-(2,6-difluorobenzoyl)-2-(4-phenoxyphenyl)-1H-pyrrole-3-carboxamide	452210: Inhibition of Csk	ic50	0.0045	uM
6-amino-7-(4-phenoxyphenyl)-9-[(3S)-1-prop-2-enoylpiperidin-3-yl]purin-8-one	1424960: 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	0.0070	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715388: Inhibition of human CSK using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0071	uM
1-[1-(tert-butylcarbamoyl)piperidin-4-yl]-N-[4-(4,5-dimethyl-6-oxo-1H-pyridazin-3-yl)-3-ethylphenyl]indazole-3-carboxamide	1512569: Inhibition of His-tagged/GST-tagged CSK (unknown origin) incubated for 1 hr by TR-FRET assay	ic50	0.0080	uM
N-[3-[2-[4-(2-aminoethoxy)anilino]quinazolin-6-yl]-4-methylphenyl]-3-(trifluoromethyl)benzamide	1799897: Fluorescence Assay from Article 10.1021/cb300623a: “A Hexylchloride-Based Catch-and-Release System for Chemical Proteomic Applications.”	ic50	0.0084	uM
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	1734770: Inhibition of human full length recombinant CSK using poly(Glu,Tyr)4:1 as substrate incubated for 40 mins in presence of [gamma33P-ATP] by radiometric scintillation counting analysis	ic50	0.0090	uM
N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-5-yl)ethyl]-4-methylbenzamide	2180123: Inhibition of CSK (unknown origin) ACT labeling site by KiNativ Profiling analysis	ic50	0.0125	uM
Ponatinib	1716391: Binding affinity to human CSK using poly[Glu:Tyr] (4:1) as substrate by radiometric hotspot kinase assay	ic50	0.0127	uM
N-[4-[(6-methoxypyrazolo[1,5-a]pyridine-3-carbonyl)amino]-3-methylphenyl]-1-methylindazole-3-carboxamide	1512574: Inhibition of CSK (unknown origin) using fluorescent labeled peptide as substrate in presence of ATP at Km concentration by caliper method	ic50	0.0130	uM
N-[3-[[3-[4-[4-[2-[[2-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]acetyl]amino]ethoxy]anilino]-1,3,5-triazin-2-yl]-2-pyridinyl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide	1799543: In Vitro Activity Assay from Article 10.1016/j.chembiol.2010.01.008: “Affinity reagents that target a specific inactive form of protein kinases.”	ic50	0.0163	uM
N-[3-[[3-[4-[4-[2-[5-[3-(2-fluoro-10,12-dimethyl-1-aza-3-azonia-2-boratricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)propanoylamino]pentanoylamino]ethoxy]anilino]-1,3,5-triazin-2-yl]-2-pyridinyl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide	1799543: In Vitro Activity Assay from Article 10.1016/j.chembiol.2010.01.008: “Affinity reagents that target a specific inactive form of protein kinases.”	kd	0.0170	uM
1-[1-(tert-butylcarbamoyl)piperidin-4-yl]-N-[4-(pyrazolo[1,5-a]pyridine-3-carbonylamino)phenyl]indazole-3-carboxamide	1512574: Inhibition of CSK (unknown origin) using fluorescent labeled peptide as substrate in presence of ATP at Km concentration by caliper method	ic50	0.0210	uM
N-[4-[[3-(dimethylamino)pyrrolidin-1-yl]methyl]-3-(trifluoromethyl)phenyl]-3-[(E)-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-5-yl)ethenyl]-4-methylbenzamide	2180123: Inhibition of CSK (unknown origin) ACT labeling site by KiNativ Profiling analysis	ic50	0.0250	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	2168199: Inhibition of human wild type CSK using PolyEY as substrate preincubated for 2 hrs followed by ATP addition and measured every 2 mins for 2.5 hrs by spectrophotometric analysis	ic50	0.0250	uM
N-[3-(2-cyanopropan-2-yl)phenyl]-3-[(E)-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-5-yl)ethenyl]-4-methylbenzamide	2180123: Inhibition of CSK (unknown origin) ACT labeling site by KiNativ Profiling analysis	ic50	0.0251	uM
3-[[4-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzamide	389069: Binding affinity to human CSK	kd	0.0280	uM
2,6-difluoro-N-[3-fluoro-4-[6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yl]oxyphenyl]benzenesulfonamide	1573289: Binding affinity to CSK in SILAC-labeled human MDA-MB-231 cells lysate by mass spectrometry based kinAffinity assay	kd	0.0300	uM
Bosutinib	624948: Binding constant for CSK kinase domain	kd	0.0320	uM
7-[4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine	213575: Inhibition of human Tyrosine-protein kinase CSK	ic50	0.0410	uM
2-[2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]-5-ethyl-1,3,4-oxadiazole	1992892: Inhibition of human recombinant CSK by microfluidic mobility shift assay	ic50	0.0540	uM
N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)benzamide	2180123: Inhibition of CSK (unknown origin) ACT labeling site by KiNativ Profiling analysis	ic50	0.0564	uM
N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[(4-methoxy-1H-pyrrolo[2,3-b]pyridin-5-yl)methoxy]-4-methylbenzamide	2180123: Inhibition of CSK (unknown origin) ACT labeling site by KiNativ Profiling analysis	ic50	0.0590	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624948: Binding constant for CSK kinase domain	kd	0.0600	uM
1-[1-(tert-butylcarbamoyl)piperidin-4-yl]-N-[3-ethyl-4-(4-methyl-6-oxo-1H-pyridazin-3-yl)phenyl]indazole-3-carboxamide	1512569: Inhibition of His-tagged/GST-tagged CSK (unknown origin) incubated for 1 hr by TR-FRET assay	ic50	0.0700	uM
1-[1-(tert-butylcarbamoyl)piperidin-4-yl]-N-[3-chloro-4-(6-oxo-1H-pyridazin-3-yl)phenyl]indazole-3-carboxamide	1512569: Inhibition of His-tagged/GST-tagged CSK (unknown origin) incubated for 1 hr by TR-FRET assay	ic50	0.0790	uM
1-[1-(tert-butylcarbamoyl)piperidin-4-yl]-N-[3-chloro-4-(4-methyl-6-oxo-1H-pyridazin-3-yl)phenyl]indazole-3-carboxamide	1512569: Inhibition of His-tagged/GST-tagged CSK (unknown origin) incubated for 1 hr by TR-FRET assay	ic50	0.0800	uM
[3-[[2-(3,5-dimorpholin-4-ylanilino)pyrimidin-4-yl]-methylamino]-4-methylphenyl]methanol	591268: Inhibition of CSK	ic50	0.0800	uM
N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[(E)-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-5-yl)ethenyl]-4-methylbenzamide	2180123: Inhibition of CSK (unknown origin) ACT labeling site by KiNativ Profiling analysis	ic50	0.0809	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	624948: Binding constant for CSK kinase domain	kd	0.1200	uM
N-[3-[[3-[6-[4-[2-[[2-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]acetyl]amino]ethoxy]anilino]pyrimidin-4-yl]-2-pyridinyl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide	1799543: In Vitro Activity Assay from Article 10.1016/j.chembiol.2010.01.008: “Affinity reagents that target a specific inactive form of protein kinases.”	ic50	0.1400	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624948: Binding constant for CSK kinase domain	kd	0.1600	uM
4-[8-amino-3-[(6R,8aS)-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721749: Inhibition of CSK (unknown origin)	ic50	0.1620	uM
1-(2-hydroxy-2-methylpropyl)-N-[5-(7-methoxyquinolin-4-yl)oxy-2-pyridinyl]-5-methyl-3-oxo-2-phenylpyrazole-4-carboxamide	343282: Inhibition of CSK	ic50	0.1650	uM
3-[2-[2-amino-5-(1-methylpyrazol-4-yl)-3-pyridinyl]ethynyl]-N-[3,5-bis(trifluoromethyl)phenyl]-4-methylbenzamide	1780018: Inhibition of human full length recombinant CSK by radiometric scintillation counting analysis	ic50	0.1870	uM
4-[8-amino-3-[(3R,6S)-1-(cyclopropanecarbonyl)-6-methylpiperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711655: Inhibition of human CSK	ic50	0.2010	uM
4-[8-amino-3-[(6R,8aS)-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-3-methoxy-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721749: Inhibition of CSK (unknown origin)	ic50	0.2270	uM
4-[8-amino-3-[(3R)-1-(3-methyloxetane-3-carbonyl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711655: Inhibition of human CSK	ic50	0.2530	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507882: Binding affinity to CSK	kd	0.2600	uM
4-[8-amino-3-[(3R)-1-(2-methoxyacetyl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488576: Inhibition of CSK (unknown origin)	ic50	0.2610	uM
N-(5-chloro-1,3-benzodioxol-4-yl)-5-(oxan-4-yloxy)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine	272223: Inhibition of recombinant CSK by ELISA	ic50	0.2700	uM
2,5-difluoro-N-[3-fluoro-4-[6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yl]oxyphenyl]benzenesulfonamide	1573289: Binding affinity to CSK in SILAC-labeled human MDA-MB-231 cells lysate by mass spectrometry based kinAffinity assay	kd	0.2700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
aristolochic acid I	increases expression	1
moringin	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
beauvericin	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
cobaltous chloride	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
cupric chloride	increases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
6-((3-chloro)anilino)-2-(isopropyl-2-hydroxyethylamino)-9-isopropylpurine	decreases activity	1
abrine	decreases expression	1
lithocholic acid acetate	decreases expression, increases reaction, increases phosphorylation	1
saracatinib	decreases expression, decreases reaction, decreases activity	1
bisphenol S	increases expression	1
ponatinib	decreases activity	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Dasatinib	affects binding	1
Sunitinib	increases expression	1
Ethanol	increases expression, affects cotreatment, increases abundance	1
Arsenic	increases abundance, increases expression	1
Atrazine	increases expression	1
Caffeine	increases phosphorylation	1

ChEMBL screening assays

535 unique, capped per target: 531 binding, 2 admet, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000661	Binding	Inhibition of CSK at 1 uM relative to control	Novel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring. — J Med Chem
CHEMBL4414992	ADMET	Inhibition of human CSK at 1 uM using poly[Glu:Tyr] (4:1) as substrate preincubated for 15 to 20 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by filter binding method	Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase. — J Med Chem
CHEMBL913341	Functional	Inhibition of CSK measured as poly-E4Y phosphorylation by acid precipitation assay in presence of 0.2 mM CoCl2	Design and evaluation of hydroxamate derivatives as metal-mediated inhibitors of a protein tyrosine kinase. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1VX	Abcam A-549 CSK KO	Cancer cell line	Male
CVCL_D2AE	Abcam HCT 116 CSK KO	Cancer cell line	Male
CVCL_SJ78	HAP1 CSK (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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