SRC

Summary

SRC (SRC proto-oncogene, non-receptor tyrosine kinase, HGNC:11283) is a protein-coding gene on chromosome 20q11.23, encoding Proto-oncogene tyrosine-protein kinase Src (P12931). Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cyt….

This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 6714 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thrombocytopenia 6 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 112 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 17
• Druggable target: yes — 103 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_198291

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11283
Approved symbol	SRC
Name	SRC proto-oncogene, non-receptor tyrosine kinase
Location	20q11.23
Locus type	gene with protein product
Status	Approved
Aliases	ASV, c-src
Ensembl gene	ENSG00000197122
Ensembl biotype	protein_coding
OMIM	190090
Entrez	6714

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 22 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000358208, ENST00000373558, ENST00000373567, ENST00000373578, ENST00000467556, ENST00000472968, ENST00000477066, ENST00000477475, ENST00000489153, ENST00000493775, ENST00000497734, ENST00000692112, ENST00000692423, ENST00000693012, ENST00000876226, ENST00000876227, ENST00000876228, ENST00000876229, ENST00000876230, ENST00000876231, ENST00000876232, ENST00000876233, ENST00000876234, ENST00000876235, ENST00000876236, ENST00000876237, ENST00000921683, ENST00000921684, ENST00000950593

RefSeq mRNA: 2 — MANE Select: NM_198291 NM_005417, NM_198291

CCDS: CCDS13294

Canonical transcript exons

ENST00000373578 — 14 exons

Exon	Start	End
ENSE00000661877	37384150	37384403
ENSE00000661879	37393895	37393993
ENSE00001460945	37346140	37346255
ENSE00001460955	37403171	37406050
ENSE00001460974	37365204	37365277
ENSE00001798147	37382619	37382786
ENSE00003516229	37397699	37397854
ENSE00003523341	37394174	37394277
ENSE00003543788	37402435	37402588
ENSE00003544319	37386075	37386174
ENSE00003564760	37400115	37400294
ENSE00003638193	37402749	37402880
ENSE00003669255	37401602	37401678
ENSE00003678936	37396162	37396311

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 95.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.5002 / max 491.3724, expressed in 1721 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184494	13.7854	1581
184493	9.4955	1658
184492	1.7431	1020
184490	1.1960	241
184491	1.0197	673
184497	0.8238	199
184496	0.2611	72
184499	0.0598	33
209101	0.0502	30
184498	0.0480	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of stomach	UBERON:0001161	95.98	gold quality
gall bladder	UBERON:0002110	95.89	gold quality
rectum	UBERON:0001052	95.58	gold quality
body of pancreas	UBERON:0001150	95.45	gold quality
lower esophagus mucosa	UBERON:0035834	95.36	gold quality
transverse colon	UBERON:0001157	95.11	gold quality
ganglionic eminence	UBERON:0004023	94.92	gold quality
cortical plate	UBERON:0005343	94.65	gold quality
stomach	UBERON:0000945	94.25	gold quality
ectocervix	UBERON:0012249	94.18	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.16	gold quality
body of uterus	UBERON:0009853	93.98	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.83	gold quality
mucosa of transverse colon	UBERON:0004991	93.62	gold quality
mucosa of stomach	UBERON:0001199	93.52	gold quality
ascending aorta	UBERON:0001496	93.25	gold quality
small intestine	UBERON:0002108	93.15	gold quality
thoracic aorta	UBERON:0001515	93.12	gold quality
right testis	UBERON:0004534	92.96	gold quality
endocervix	UBERON:0000458	92.93	gold quality
esophagus mucosa	UBERON:0002469	92.91	gold quality
ventricular zone	UBERON:0003053	92.88	gold quality
metanephros cortex	UBERON:0010533	92.86	gold quality
left testis	UBERON:0004533	92.75	gold quality
right adrenal gland cortex	UBERON:0035827	92.73	gold quality
right adrenal gland	UBERON:0001233	92.60	gold quality
right ovary	UBERON:0002118	92.56	gold quality
left adrenal gland	UBERON:0001234	92.48	gold quality
left uterine tube	UBERON:0001303	92.48	gold quality
left adrenal gland cortex	UBERON:0035825	92.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.16

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, ARNT, EGR1, ESR1, ESR2, FOXO3, GTF2I, HHEX, HIF1A, HNF1A, HNF4A, IER2, JDP2, JUN, JUNB, KAT7, MAFB, NCOA1, NCOA2, NCOA3, NFATC1, NFIC, NFKB, RBPJ, RELA, RELB, SP1, SP3, STAT5A, TAF1, THRA

miRNA regulators (miRDB)

85 targeting SRC, 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-3064-3P	100.00	70.09	1254
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-488-3P	99.61	68.79	1731

Literature-anchored findings (GeneRIF, showing 40)

• Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton. (PMID:11940607)
• v-Src’s hold over actin and cell adhesions. (PMID:11994743)
• PLD1 is threonine-phosphorylated in human-airway epithelial cells by a PKCdelta and src dependent mechanism (PMID:12014986)
• The Src-cortactin pathway is required for clustering of E-selectin and ICAM-1 in endothelial cells (PMID:12060669)
• Activation of a Src-dependent Raf-MEK1/2-ERK signaling pathway is required for IL-1alpha-induced upregulation of beta-defensin 2 in human middle ear epithelial cells. (PMID:12063167)
• REVIEW: Arsenic carcinogenicity: relevance of c-Src activation (PMID:12162444)
• Functional involvement of src and focal adhesion kinase in a CD99 splice variant-induced motility of human breast cancer cells (PMID:12216109)
• The p85 subunit of PI 3-kinase activates Src independently of the enzymatic activity of PI 3- kinase. Ligand binding of GPIb, without receptor clustering, is sufficient to activate Src. (PMID:12393736)
• pp60c-src may be involved in stabilization of dynamic HT-29 cell adhesion to ECM components, and this kinase appears to be part of a mechanosensory protein complex during integrin-mediated cell adhesion (PMID:12416028)
• Src activation may contribute to colon tumor progression and metastasis in part by activating Akt-mediated survival pathways that decrease sensitivity of detached cells to anoikis. (PMID:12420216)
• mediation of synergism with epidermal growth factor receptor by STAT5b (PMID:12429742)
• Data report a novel positioning of Src, mediating signals from insulin to phosphatidylinositol 3-kinase and to beta(2)-adrenergic receptor trafficking. (PMID:12429837)
• Mutual interaction of c-Src with EGFR is required for many EGFR-mediated cellular functions including proliferation, migration, survival and EGFR endocytosis, as discussed in this review. (PMID:12456372)
• c-Src activation is associated with early stages of breast carcinomas with low aggressiveness. (PMID:12462387)
• src has a role in promoting destruction of c-Cbl and enabling EGFR to evade desensitization as part of an oncogenesis pathway (PMID:12604776)
• c-Src, lacking cysteine at position 520, is resistant to 1 microM N-(9-acridinyl) maleimide (NAM) but sensitive to 5 microM. Changing Phe520 to cysteine made it sensitive to 1 microM. Double mutation in clustered cysteines restored resistance to 5 microM. (PMID:12618767)
• Results demonstrate that c-Src and TRAF6 are key mediators of interleukin-1-induced AP-1 activation and provide evidence of cross talk between c-Src and TRAF6 molecules through PI3 kinase-Akt-JNK pathways. (PMID:12631284)
• c-Src regulates NAD(P)H oxidase-derived *O2- generation acutely by stimulating p47phox phosphorylation and translocation and chronically by increasing protein content of gp91phox, p22phox, and p47phox in Ang II-stimulated cells. (PMID:12663375)
• stimulated by HBX protein acting on the mitochondrial transition pore and effecting hepatitis B virus replication. (PMID:12829810)
• involvement of G(i), Src tyrosine kinase and PI3 Kinase, respectively, in TNFalpha production (PMID:12842760)
• v-SRC regulates the nucleo-cytoplasmic delocalization of the major isoform of TEL-ETV6 (PMID:12893822)
• role of c-Src on PRL-stimulated proliferation of T47D and MCF7 breast cancer cells (PMID:12907754)
• FAK and Src are both important survival factors, playing a role in protecting colon cancer cell lines from Adenovirus-containing FAK-CD (Ad-FAK-CD)-induced apoptosis (PMID:12939401)
• Inhibition of Src signaling results in a marked reduction of pancreatic cancer cellular invasiveness. Src may represent a novel therapeutic target for this deadly cancer. (PMID:12947321)
• Src has an appreciable role in the organization of the Golgi apparatus, which may be linked to its involvement in protein transport from the Golgi apparatus to the endoplasmic reticulum (PMID:12975382)
• SRC tyrosine kinases are activated and have a role in tyrosine phosphorylation of ezrin and activation of p38 (PMID:14504278)
• c-src activation of PLCgamma is mediated by GIT1 (PMID:14523024)
• The data indicate an increase in the expression and total activity of endogenous p60(c-Src) in several GM-CSF-independent 1 cultured leukemia cell mutants. (PMID:14562045)
• focal adhesion kinase and src are stimulated by G alpha q and platelet activating factor receptor in vascular endothelium (PMID:14617636)
• role of IGF-1R and c-Src in human pancreatic carcinogenesis. Coexpression of both these molecules may play important role in transformation of pancreatic ductal cells. (PMID:14627343)
• data suggest that agonist-induced binding of Src kinase to the Src homology 3 binding sites in the P2Y(2) purinergic receptor facilitates Src activation and allows Src to efficiently phosphorylate the epidermal growth factor receptor (PMID:14670955)
• A novel regulatory network RAFTK/Pyk2, Src and p38 appears to be critical for VEGF-induced endothelial cell migration. (PMID:14676843)
• v-Src and receptor tyrosine kinase ErbB2 activate beta-catenin-TCF-mediated transcription. (PMID:14706618)
• Ret tyrosine 981 constitutes the major binding site of the Src homology 2 domain of Src and therefore the primary residue responsible for Src activation upon Ret engagement (PMID:14766744)
• EGFR and c-Src-mediated Stat-3 activation is facilitated by Pyk2 (PMID:14963038)
• src and protein kinase C have roles in inducing phosphorylation of p38 mitogen-activated protein kinase in epithelial cells after mechanical pressure (PMID:15033452)
• mechanisms of c-Src activation in human cancer (review) (PMID:15060621)
• both the androgen receptor interacting domains of the coactivator SRC1 and of the corepressor SMRT compete for interaction with the androgen receptor N-terminus (PMID:15062576)
• SH2 and SH3 domains of Src mediate peripheral accumulation of phospho-myosin, leading to integrin adhesion complex assembly, whereas loss of SH2 or SH3 function restores normal regulation of E-cadherin and inhibits vimentin expression (PMID:15075377)
• hTAF(II)68-mediated transactivation is linked to the cytoplasmic Src signal transduction pathway. The hTAF(II)68 protein can associate with the SH3 domains of several cell signaling proteins, including v-Src. (PMID:15094065)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	src	ENSDARG00000008107
mus_musculus	Src	ENSMUSG00000027646
rattus_norvegicus	Src	ENSRNOG00000009495

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), CSK (ENSG00000103653), TYK2 (ENSG00000105397), JAK3 (ENSG00000105639), FRK (ENSG00000111816), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), SYK (ENSG00000165025), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), FES (ENSG00000182511), LCK (ENSG00000182866), LYN (ENSG00000254087)

Protein

Protein identifiers

Proto-oncogene tyrosine-protein kinase Src — P12931 (reviewed: P12931)

Alternative names: Proto-oncogene c-Src, pp60c-src

All UniProt accessions (2): A0A8I5KYU4, P12931

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1. Phosphorylates PKP3 at ‘Tyr-195’ in response to reactive oxygen species, which may cause the release of PKP3 from desmosome cell junctions into the cytoplasm. Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors. Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated calcium-activated chloride channel activation. Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at ‘Tyr-1477’. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus. Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. Upon activation of the G(q)-dependent KISS1/KISS1R signaling pathway, active SRC is recruited, together with the phosphatase DUSP18, to the KISS1R C-terminus. This leads to DUSP18-mediated SRC dephosphorylation and inactivation, down-regulation of osteoclast differentiation and activity, and consequently suppression of bone resorption. Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase. Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on ‘Tyr-284’ and CBL on ‘Tyr-731’. Enhances RIGI-elicited antiviral signaling. Phosphorylates PDPK1 at ‘Tyr-9’, ‘Tyr-373’ and ‘Tyr-376’. Phosphorylates BCAR1 at ‘Tyr-128’. Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at ‘Tyr-341’ activates CBLC E3 activity. Phosphorylates synaptic vesicle protein synaptophysin (SYP). Involved in anchorage-independent cell growth. Required for podosome formation. Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration. Phosphorylates OTUB1, promoting deubiquitination of RPTOR. Phosphorylates caspase CASP8 at ‘Tyr-380’ which negatively regulates CASP8 processing and activation, down-regulating CASP8 proapoptotic function. Mediates laminin-induced activation of RAC1 signaling through phosphorylation of syntrophin. Non-receptor protein tyrosine kinase which phosphorylates synaptophysin with high affinity. Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation. The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity. Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs. Plays a role in L1CAM-mediated neurite elongation, possibly by acting downstream of L1CAM to drive cytoskeletal rearrangements involved in neurite outgrowth. Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation. The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity. Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs. Plays a role in neurite elongation.

Subunit / interactions. Part of a complex comprised of PTPRA, BCAR1, BCAR3 (via SH2 domain) and SRC; the formation of the complex is dependent on integrin mediated-tyrosine phosphorylation of PTPRA. Interacts with DDEF1/ASAP1; via the SH3 domain. Interacts with CCPG1. Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts with ERBB2, STAT1 and PNN. Interacts with DDR1, DDR2 and DAB2. Interacts with CDCP1, TGFB1I1 and TOM1L2. Interacts with the cytoplasmic domain of MUC1, phosphorylates it and increases binding of MUC1 with beta-catenin. Interacts with RALGPS1; via the SH3 domain. Interacts with CAV2 (tyrosine phosphorylated form). Interacts (via the SH3 domain and the protein kinase domain) with ARRB1; the interaction is independent of the phosphorylation state of SRC C-terminus. Interacts with ARRB1 and ARRB2. Interacts with SRCIN1. Interacts with NDFIP2 and more weakly with NDFIP1. Interacts with PIK3CA and/or PIK3C2B, PTK2/FAK1 and ESR1 (dimethylated on arginine). Interacts with FASLG. Interacts (via SH2 domain) with the ‘Tyr-402’ phosphorylated form of PTK2B/PYK2. Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with PDGFRA (tyrosine phosphorylated). Interacts with CSF1R. Interacts (via SH2 and SH3 domain) with TNK2. Interacts (via protein kinase domain) with the tyrosine phosphorylated form of RUNX3 (via runt domain). Interacts with TRAF3 (via RING-type zinc finger domain). Interacts with RIGI, MAVS and TBK1. Interacts (via SH2 domain) with RACK1; the interaction is enhanced by tyrosine phosphorylation of RACK1 and inhibits SRC activity. Interacts with EPHB1; activates the MAPK/ERK cascade to regulate cell migration. Interacts with FCAMR. Interacts (via SH2 domain) with the ‘Tyr-9’ phosphorylated form of PDPK1. Interacts with AMOTL2; this interaction regulates the translocation of phosphorylated SRC to peripheral cell-matrix adhesion sites. Interacts with TRAP1. Interacts with CBLC; the interaction is enhanced when SRC is phosphorylated at Tyr-419. Interacts with ARHGEF5. Interacts (via cytoplasmic domain) with CEACAM1 (via SH2 domain); this interaction is regulated by trans-homophilic cell adhesion. Interacts with MPP2. Interacts with PRR7. Interacts (via kinase domain and to a lesser extent the SH2 domain) directly with PDLIM4; this interaction results in PTPN13-mediated dephosphorylation of this protein leading to its inactivation. Interacts with P85 (PIK3R1 or PIK3R2). Interacts with HNRNPA2B1. Interacts with IL6ST/gp130. Interacts (via SH3 domain) with PELP1 in the presence of 17-beta-estradiol. Interacts with AMBRA1. Interacts with KISS1R and DUSP18; the interaction depends on activation of KISS1/KISS1R signaling pathway. Interaction with KISS1R and DUSP18 is required for SRC dephosphorylation and inactivation, and down-regulation of osteoclast activity and bone resorption. (Microbial infection) Interacts with HEV ORF3 protein; via the SH3 domain. (Microbial infection) Interacts (via SH2 domain) with HCV non-structural protein 5A (via N-terminus).

Subcellular location. Cell membrane. Mitochondrion inner membrane. Nucleus. Cytoplasm. Cytoskeleton. Perinuclear region. Cell junction. Focal adhesion.

Tissue specificity. Expressed ubiquitously. Expressed in the skin (at protein level). Platelets, neurons and osteoclasts express 5-fold to 200-fold higher levels than most other tissues. Expressed in spleen and liver. Expressed in brain. Expressed in brain.

Post-translational modifications. Myristoylated at Gly-2, and this is essential for targeting to membranes. Dephosphorylated at Tyr-530 by PTPRJ. Phosphorylated on Tyr-530 by c-Src kinase (CSK). The phosphorylated form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-419. Normally maintained in an inactive conformation with the SH2 domain engaged with Tyr-530, the SH3 domain engaged with the SH2-kinase linker, and Tyr-419 dephosphorylated. Dephosphorylation of Tyr-530 as a result of protein tyrosine phosphatase (PTP) action disrupts the intramolecular interaction between the SH2 domain and Tyr-530, Tyr-419 can then become autophosphorylated, resulting in SRC activation. Phosphorylation of Tyr-530 by CSK allows this interaction to reform, resulting in SRC inactivation. CDK5-mediated phosphorylation at Ser-75 targets SRC to ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. Phosphorylated by PTK2/FAK1; this enhances kinase activity. Phosphorylated by PTK2B/PYK2; this enhances kinase activity. Upon activation of IL6ST by IL6, Tyr-419 is phosphorylated and Tyr-530 dephosphorylated. Displays reduced levels of autophosphorylation at Tyr-419 compared to isoforms 2 and 3. Displays enhanced levels of autophosphorylation at Tyr-419 compared to isoform 1. Displays enhanced levels of autophosphorylation at Tyr-419 compared to isoform 1. Shows reduced phosphorylation at Tyr-527 compared to isoforms 1 and 2. S-nitrosylation is important for activation of its kinase activity. Ubiquitinated in response to CDK5-mediated phosphorylation. Ubiquitination mediated by CBLC requires SRC autophosphorylation at Tyr-419 and may lead to lysosomal degradation.

Disease relevance. SRC kinase activity has been shown to be increased in several tumor tissues and tumor cell lines such as colon carcinoma cells. Thrombocytopenia 6 (THC6) [MIM:616937] A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC6 is an autosomal dominant form. Affected individuals may also have bone abnormalities and an increased risk for myelofibrosis. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Phosphorylation by CSK at Tyr-530 inhibits kinase activity. Inhibitory phosphorylation at Tyr-530 is enhanced by heme. Further phosphorylation by CDK1 partially reactivates CSK-inactivated SRC and facilitates complete reactivation by protein tyrosine phosphatase PTPRC. Integrin engagement stimulates kinase activity. Phosphorylation by PTK2/FAK1 enhances kinase activity. Butein and pseudosubstrate-based peptide inhibitors like CIYKYYF act as inhibitors. Phosphorylation at Tyr-419 increases kinase activity.

Domain organisation. The SH2 and SH3 domains are important for the intramolecular and intermolecular interactions that regulate catalytic activity, localization, and substrate recruitment.

Miscellaneous. May be involved in blister formation in Pemphigus vulgaris, phosphorylated-SRC is abundant at blister sites but not in normally adherent tissue, which corresponds with loss and disruption of CDH1 in cells adjacent to blisters. Phosphorylated SRC is increasingly abundant at pre-lesional sites of blister formation and occurs prior to changes in abundance of CDH1 and DSG3.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P12931-1	1, c-src	yes
P12931-2	2, c-srcN1, N1-Src
P12931-3	3, c-srcN2, N2-Src

RefSeq proteins (2): NP_005408, NP_938033* (*=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
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 (80 total): strand 27, helix 20, turn 7, modified residue 6, mutagenesis site 4, sequence variant 3, domain 3, splice variant 2, binding site 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

79 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9OFX	X-RAY DIFFRACTION	1.45
1FMK	X-RAY DIFFRACTION	1.5
1O43	X-RAY DIFFRACTION	1.5
1O4A	X-RAY DIFFRACTION	1.5
1O4R	X-RAY DIFFRACTION	1.5
2SRC	X-RAY DIFFRACTION	1.5
6C4S	X-RAY DIFFRACTION	1.5
7NG7	X-RAY DIFFRACTION	1.5
8VCF	X-RAY DIFFRACTION	1.5
1O48	X-RAY DIFFRACTION	1.55
1O4G	X-RAY DIFFRACTION	1.55
1O4K	X-RAY DIFFRACTION	1.57
4F5B	X-RAY DIFFRACTION	1.57
1O4M	X-RAY DIFFRACTION	1.6
1O4N	X-RAY DIFFRACTION	1.6
8VCG	X-RAY DIFFRACTION	1.61
1O4L	X-RAY DIFFRACTION	1.65
1O41	X-RAY DIFFRACTION	1.7
1O42	X-RAY DIFFRACTION	1.7
1O44	X-RAY DIFFRACTION	1.7
1O49	X-RAY DIFFRACTION	1.7
1O4J	X-RAY DIFFRACTION	1.7
1O4O	X-RAY DIFFRACTION	1.7
1O4Q	X-RAY DIFFRACTION	1.7
4F59	X-RAY DIFFRACTION	1.71
1O4I	X-RAY DIFFRACTION	1.75
1O45	X-RAY DIFFRACTION	1.8
1O47	X-RAY DIFFRACTION	1.8
1O4C	X-RAY DIFFRACTION	1.8
3VRO	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P12931-F1	84.59	0.68

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): 389 (proton acceptor)

Ligand- & substrate-binding residues (2): 276–284; 298

Post-translational modifications (7): 17, 75, 187, 419, 419, 530, 2

Mutagenesis-validated functional residues (4):

Position	Phenotype
298	kinase inactive. abolishes ubiquitination promoted by cblc.
302	kinase active. interacts with pdlim4; when associated with e-307 and f-419.
307	kinase active. interacts with pdlim4; when associated with e-302 and f-419.
419	loss of kinase activity. loss of interaction with pdlim4.

Function

Pathways and Gene Ontology

Reactome pathways

121 pathways

ID	Pathway
R-HSA-1227986	Signaling by ERBB2
R-HSA-1251985	Nuclear signaling by ERBB4
R-HSA-1253288	Downregulation of ERBB4 signaling
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-180292	GAB1 signalosome
R-HSA-186763	Downstream signal transduction
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-354192	Integrin signaling
R-HSA-354194	GRB2:SOS provides linkage to MAPK signaling for Integrins
R-HSA-372708	p130Cas linkage to MAPK signaling for integrins
R-HSA-418555	G alpha (s) signalling events
R-HSA-418594	G alpha (i) signalling events
R-HSA-418885	DCC mediated attractive signaling
R-HSA-418886	Netrin mediated repulsion signals
R-HSA-428542	Regulation of commissural axon pathfinding by SLIT and ROBO
R-HSA-5673000	RAF activation
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-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8874081	MET activates PTK2 signaling
R-HSA-8876493	InlA-mediated entry of Listeria monocytogenes into host cells
R-HSA-8934593	Regulation of RUNX1 Expression and Activity
R-HSA-8940973	RUNX2 regulates osteoblast differentiation
R-HSA-8941858	Regulation of RUNX3 expression and activity
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9013420	RHOU GTPase cycle
R-HSA-9032500	Activated NTRK2 signals through FYN

MSigDB gene sets: 945 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_CHROMOSOME_ORGANIZATION, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_GLAND_MORPHOGENESIS

GO Biological Process (94): negative regulation of transcription by RNA polymerase II (GO:0000122), stimulatory C-type lectin receptor signaling pathway (GO:0002223), negative regulation of inflammatory response to antigenic stimulus (GO:0002862), cell adhesion (GO:0007155), signal transduction (GO:0007165), signal complex assembly (GO:0007172), epidermal growth factor receptor signaling pathway (GO:0007173), transforming growth factor beta receptor signaling pathway (GO:0007179), integrin-mediated signaling pathway (GO:0007229), regulation of epithelial cell migration (GO:0010632), positive regulation of epithelial cell migration (GO:0010634), positive regulation of protein processing (GO:0010954), macroautophagy (GO:0016236), peptidyl-tyrosine phosphorylation (GO:0018108), regulation of cell-cell adhesion (GO:0022407), cell differentiation (GO:0030154), platelet activation (GO:0030168), forebrain development (GO:0030900), T cell costimulation (GO:0031295), negative regulation of protein-containing complex assembly (GO:0031333), protein destabilization (GO:0031648), negative regulation of telomere maintenance (GO:0032205), regulation of intracellular estrogen receptor signaling pathway (GO:0033146), positive regulation of integrin activation (GO:0033625), regulation of toll-like receptor 3 signaling pathway (GO:0034139), substrate adhesion-dependent cell spreading (GO:0034446), cellular response to reactive oxygen species (GO:0034614), positive regulation of Rac protein signal transduction (GO:0035022), positive regulation of dephosphorylation (GO:0035306), negative regulation of hippo signaling (GO:0035331), intracellular signal transduction (GO:0035556), osteoclast development (GO:0036035), cellular response to platelet-derived growth factor stimulus (GO:0036120), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), ERBB2 signaling pathway (GO:0038128), angiotensin-activated signaling pathway (GO:0038166), vasodilation (GO:0042311), odontogenesis (GO:0042476), negative regulation of apoptotic process (GO:0043066), regulation of vascular permeability (GO:0043114)

GO Molecular Function (27): protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), signaling receptor binding (GO:0005102), integrin binding (GO:0005178), ATP binding (GO:0005524), phospholipase activator activity (GO:0016004), enzyme binding (GO:0019899), heme binding (GO:0020037), protein tyrosine kinase activator activity (GO:0030296), signaling receptor activator activity (GO:0030546), ionotropic glutamate receptor binding (GO:0035255), SH2 domain binding (GO:0042169), phospholipase binding (GO:0043274), transmembrane transporter binding (GO:0044325), cadherin binding (GO:0045296), ephrin receptor binding (GO:0046875), ATPase binding (GO:0051117), phosphoprotein binding (GO:0051219), BMP receptor binding (GO:0070700), connexin binding (GO:0071253), scaffold protein binding (GO:0097110), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), protein domain specific binding (GO:0019904)

GO Cellular Component (21): podosome (GO:0002102), nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), lysosome (GO:0005764), late endosome (GO:0005770), cytosol (GO:0005829), actin filament (GO:0005884), plasma membrane (GO:0005886), caveola (GO:0005901), cell-cell junction (GO:0005911), focal adhesion (GO:0005925), cell junction (GO:0030054), ruffle membrane (GO:0032587), membrane raft (GO:0045121), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), cytoskeleton (GO:0005856), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Oncogenic MAPK signaling	3
Signaling by ERBB4	2
Integrin signaling	2
GPCR downstream signalling	2
Netrin-1 signaling	2
RAF/MAP kinase cascade	2
Signaling by Receptor Tyrosine Kinases	1
Intracellular signaling by second messengers	1
Signaling by EGFR	1
Signaling by PDGF	1
PI3K/AKT Signaling in Cancer	1
Signal Transduction	1
Platelet Aggregation (Plug Formation)	1
Signaling by ROBO receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein binding	4
cytoplasm	3
cellular process	2
protein-containing complex assembly	2
epithelial cell migration	2
protein tyrosine kinase activity	2
signaling receptor binding	2
cell adhesion molecule binding	2
enzyme binding	2
intracellular membrane-bounded organelle	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
innate immune response activating cell surface receptor signaling pathway	1
cellular response to lectin	1
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1
negative regulation of immune response	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of signal transduction	1
ERBB signaling pathway	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell surface receptor signaling pathway	1
regulation of cell migration	1
regulation of multicellular organismal process	1
regulation of epithelial cell migration	1
positive regulation of cell migration	1
protein processing	1
positive regulation of proteolysis	1
regulation of protein processing	1
positive regulation of protein maturation	1
autophagosome assembly	1
autophagy	1
protein phosphorylation	1

Protein interactions and networks

STRING

9720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRC	PXN	P49023	998
SRC	BCAR1	P56945	998
SRC	CTTN	Q14247	997
SRC	STAT3	P40763	996
SRC	TLN1	Q9Y490	996
SRC	ESR1	P03372	996
SRC	VCL	P18206	995
SRC	CRK	P46108	995
SRC	ARRB1	P49407	995
SRC	HCLS1	P14317	994
SRC	HSP90AA1	P07900	994
SRC	CAV1	Q03135	994
SRC	TLN2	Q9Y4G6	994
SRC	CBL	P22681	993
SRC	HSP90AB1	P08238	993

IntAct

801 interactions, top by confidence:

A	B	Type	Score
PTK2	SRC	psi-mi:“MI:0915”(physical association)	0.920
EGFR	SRC	psi-mi:“MI:0915”(physical association)	0.910
ACBD6	NMT2	psi-mi:“MI:0214”(myristoylation reaction)	0.870
ACBD6	NMT2	psi-mi:“MI:0211”(lipid addition)	0.870
ESR1	SRC	psi-mi:“MI:0914”(association)	0.850
SRC	ESR1	psi-mi:“MI:0914”(association)	0.850
KDR	SRC	psi-mi:“MI:0915”(physical association)	0.770
SRC	KDR	psi-mi:“MI:0915”(physical association)	0.770
ADAM15	SRC	psi-mi:“MI:0407”(direct interaction)	0.750
SRC	CDC37	psi-mi:“MI:0915”(physical association)	0.710
SRC	LYN	psi-mi:“MI:0914”(association)	0.670
HSP90AA1	SRC	psi-mi:“MI:0915”(physical association)	0.670
MED28	SRC	psi-mi:“MI:0915”(physical association)	0.660
JMJD6	ESR1	psi-mi:“MI:0914”(association)	0.650
PAG1	LYN	psi-mi:“MI:0914”(association)	0.640
PIK3R3	SRC	psi-mi:“MI:0915”(physical association)	0.620
SRC	PIK3R3	psi-mi:“MI:0915”(physical association)	0.620
ARRB1	SRC	psi-mi:“MI:0915”(physical association)	0.620
ARRB1	SRC	psi-mi:“MI:0914”(association)	0.620
	NMT2	psi-mi:“MI:0214”(myristoylation reaction)	0.620
	NMT2	psi-mi:“MI:0211”(lipid addition)	0.620
ASAP1	SRC	psi-mi:“MI:0915”(physical association)	0.610

BioGRID (1087): SPRR2A (Reconstituted Complex), SPRR2A (Affinity Capture-Western), CA3 (Two-hybrid), ARRB2 (Affinity Capture-Western), SRC (Affinity Capture-Western), NEDD4 (Reconstituted Complex), NEDD4 (Biochemical Activity), MAPT (Biochemical Activity), SRC (Reconstituted Complex), SRC (Affinity Capture-Western), SRC (Reconstituted Complex), SRC (Co-localization), ESR1 (Co-localization), PSMB9 (Co-localization), POLR2A (Co-localization)

ESM2 similar proteins: A0JNB0, A1A5H8, A1Y2K1, F1LM93, F1RDG9, P00523, P00524, P00525, P00526, P00527, P05480, P06239, P06240, P06241, P07947, P07948, P08103, P08631, P09324, P09769, P10936, P12931, P13115, P13116, P13406, P14084, P14085, P14234, P17713, P25020, P27446, P27447, P31693, P39688, P42683, P50545, P63185, Q01621, Q02977, Q04736

Diamond homologs: A0JNB0, A1A5H8, A1Y2K1, F1LM93, F1RDG9, G5EE56, O45539, P00519, P00520, P00521, P00522, P00523, P00524, P00525, P00526, P00527, P00528, P00544, P03949, P05480, P06239, P06240, P06241, P07947, P07948, P08103, P08630, P08631, P09324, P09769, P10447, P10936, P12931, P13115, P13116, P13406, P14084, P14085, P14234, P15054

SIGNOR signaling

200 interactions.

A	Effect	B	Mechanism
SRC	“up-regulates activity”	BCAR1	phosphorylation
SRC	“up-regulates activity”	IKBKB	phosphorylation
DOK4	up-regulates	SRC	binding
SRC	“up-regulates activity”	LRP1	phosphorylation
SRC	down-regulates	DAG1	phosphorylation
SRC	down-regulates	TERT	phosphorylation
SRC	up-regulates	TIAM1	phosphorylation
PTPN1	up-regulates	SRC	dephosphorylation
SRC	down-regulates	PTEN	phosphorylation
SRC	“up-regulates activity”	PLSCR1	phosphorylation
SRC	“up-regulates activity”	KIT	phosphorylation
SRC	“up-regulates activity”	CTNNB1	phosphorylation
SRC	“down-regulates activity”	CTNNB1	phosphorylation
SRC	“up-regulates activity”	PDPK1	phosphorylation
SRC	up-regulates	STAT5A	phosphorylation
SRC	“down-regulates activity”	RRAS	phosphorylation
SRC	“up-regulates activity”	PTPRA	phosphorylation
SRC	up-regulates	PRKCI	phosphorylation
SRC	up-regulates	MPZL1	phosphorylation
herbimycin	down-regulates	SRC	“chemical inhibition”
PP2	down-regulates	SRC	“chemical inhibition”
SRC	up-regulates	MAPK7
PRKACA	up-regulates	SRC	phosphorylation
SRC	up-regulates	KCNA3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 142 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
Constitutive Signaling by EGFRvIII	6	39.6×	3e-06
Signaling by ERBB2 ECD mutants	6	37.3×	3e-06
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	6	31.7×	6e-06
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	6	28.8×	8e-06
Role of LAT2/NTAL/LAB on calcium mobilization	5	27.8×	6e-05
Signaling by ERBB2 KD Mutants	6	23.5×	2e-05
Regulation of signaling by CBL	5	23.0×	1e-04
Signaling by ERBB2 TMD/JMD mutants	5	22.0×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	10	18.8×	2e-07
ephrin receptor signaling pathway	5	13.0×	5e-03
bone development	6	12.6×	2e-03
cell surface receptor protein tyrosine kinase signaling pathway	9	11.8×	5e-05
insulin receptor signaling pathway	6	10.1×	5e-03
modulation of chemical synaptic transmission	7	9.7×	2e-03
positive regulation of cell growth	6	8.3×	7e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	11	6.5×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	43
Likely benign	18
Benign	23

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
12573	NM_198291.3(SRC):c.1591C>T (p.Gln531Ter)	Pathogenic
225689	NM_198291.3(SRC):c.1579G>A (p.Glu527Lys)	Likely pathogenic

SpliceAI

3484 predictions. Top by Δscore:

Variant	Effect	Δscore
20:37382617:A:AG	acceptor_gain	1.0000
20:37382618:G:GG	acceptor_gain	1.0000
20:37384148:A:AG	acceptor_gain	1.0000
20:37384149:G:GG	acceptor_gain	1.0000
20:37384149:GGA:G	acceptor_gain	1.0000
20:37384149:GGACC:G	acceptor_gain	1.0000
20:37386073:AGGT:A	acceptor_gain	1.0000
20:37386074:GGTG:G	acceptor_gain	1.0000
20:37386170:AACAC:A	donor_gain	1.0000
20:37386171:ACAC:A	donor_gain	1.0000
20:37386172:CAC:C	donor_gain	1.0000
20:37386172:CACG:C	donor_loss	1.0000
20:37386173:AC:A	donor_gain	1.0000
20:37386174:CG:C	donor_loss	1.0000
20:37386175:G:GG	donor_gain	1.0000
20:37386176:TGAG:T	donor_loss	1.0000
20:37393888:T:TA	acceptor_gain	1.0000
20:37393894:GA:G	acceptor_gain	1.0000
20:37393991:GGA:G	donor_gain	1.0000
20:37393992:GAG:G	donor_gain	1.0000
20:37393994:G:GG	donor_gain	1.0000
20:37394170:CCAG:C	acceptor_loss	1.0000
20:37394171:CAG:C	acceptor_loss	1.0000
20:37394172:AGGT:A	acceptor_gain	1.0000
20:37394173:G:A	acceptor_loss	1.0000
20:37394173:GGTG:G	acceptor_gain	1.0000
20:37396307:CTCCA:C	donor_gain	1.0000
20:37396308:TCCA:T	donor_gain	1.0000
20:37396308:TCCAG:T	donor_loss	1.0000
20:37396309:CCA:C	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000006653 (20:37356157 G>A), RS1000046462 (20:37396568 T>C), RS1000092949 (20:37345905 G>C,T), RS1000098870 (20:37402370 G>A), RS1000179323 (20:37350338 A>G), RS1000215619 (20:37381019 C>T), RS1000239375 (20:37372425 T>C), RS1000284761 (20:37379667 T>C), RS1000324335 (20:37385428 C>G,T), RS1000332169 (20:37368318 T>C), RS1000376862 (20:37385110 A>C,G,T), RS1000396840 (20:37342856 C>T), RS1000432852 (20:37378056 T>A), RS1000509041 (20:37362584 C>T), RS1000520364 (20:37351798 G>A)

Disease associations

OMIM: gene MIM:190090 | disease phenotypes: MIM:166710, MIM:254450, MIM:616937, MIM:616579

GenCC curated gene-disease

Disease	Classification	Inheritance
thrombocytopenia 6	Strong	Autosomal dominant
colorectal cancer	No Known Disease Relationship	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
thrombocytopenia 6	Moderate	AD

Mondo (6): thrombocytopenia (MONDO:0002049), osteoporosis (MONDO:0005298), primary myelofibrosis (MONDO:0009692), thrombocytopenia 6 (MONDO:0014837), intellectual disability, autosomal dominant 40 (MONDO:0014699), colorectal cancer (MONDO:0005575)

Orphanet (3): Hereditary thrombocytopenia with early-onset myelofibrosis (Orphanet:480851), Primary myelofibrosis (Orphanet:824), CHAMP1-related intellectual disability-facial dysmorphism-behavioral abnormalities syndrome (Orphanet:692193)

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000490	Deeply set eye
HP:0000601	Hypotelorism
HP:0000939	Osteoporosis
HP:0001442	Typified by somatic mosaicism
HP:0001873	Thrombocytopenia
HP:0001892	Abnormal bleeding
HP:0002003	Large forehead
HP:0002891	Uterine leiomyosarcoma
HP:0003003	Colon cancer
HP:0004406	Spontaneous, recurrent epistaxis
HP:0005584	Renal cell carcinoma
HP:0006716	Hereditary nonpolyposis colorectal carcinoma
HP:0006740	Transitional cell carcinoma of the bladder
HP:0006753	Neoplasm of the stomach
HP:0011974	Myelofibrosis
HP:0031020	Bone marrow hypercellularity

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001854_10	Retinopathy in non-diabetics	4.000000e-06
GCST003422_3	Squamous cell carcinoma	1.000000e-06
GCST007843_28	Rheumatoid arthritis	4.000000e-13
GCST012488_42	L1-L4 bone mineral density x serum urate levels interaction	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0007701	spine bone mineral density

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D010024	Osteoporosis	C05.116.198.579; C18.452.104.579
D055728	Primary Myelofibrosis	C15.378.190.636.765
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL2111336 (SELECTIVITY GROUP), CHEMBL2363074 (PROTEIN FAMILY), CHEMBL267 (SINGLE PROTEIN), CHEMBL3885535 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523733 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523978 (SELECTIVITY GROUP), CHEMBL4630728 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

103 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 336,985 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289494	TIVOZANIB	4	4,455
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1421	DASATINIB ANHYDROUS	4	55,003
CHEMBL1448	NICLOSAMIDE	4	14,322
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	285
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL2110732	DACOMITINIB ANHYDROUS	4	6,578
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL4298138	REPOTRECTINIB	4	1,038
CHEMBL477772	PAZOPANIB	4
CHEMBL502835	NINTEDANIB	4
CHEMBL535	SUNITINIB	4
CHEMBL5416410	DASATINIB	4
CHEMBL553	ERLOTINIB	4
CHEMBL554	LAPATINIB	4
CHEMBL571546	TIRBANIBULIN	4
CHEMBL601719	CRIZOTINIB	4
CHEMBL608533	MIDOSTAURIN	4
CHEMBL752	ADENOSINE PHOSPHATE	4

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Src family

Most potent curated ligand interactions (28 total), top 25:

Ligand	Action	Affinity	Parameter
elzovantinib	Inhibition	9.85	pIC50
eCF506	Inhibition	9.3	pIC50
dasatinib	Inhibition	9.1	pIC50
bosutinib	Inhibition	9.0	pIC50
compound 2 [PMID: 15546730]	Inhibition	9.0	pIC50
dorsomorphin	Inhibition	8.7	pIC50
saracatinib	Inhibition	8.57	pIC50
nefextinib	Inhibition	8.22	pIC50
WH-4-023	Inhibition	8.22	pIC50
PD166285	Inhibition	8.08	pKi
CCT241161	Inhibition	8.0	pIC50
PP121	Inhibition	7.85	pIC50
ibrutinib	Inhibition	7.72	pIC50
ENMD-2076	Inhibition	7.7	pIC50
CCT196969	Inhibition	7.52	pIC50
compound 8h [PMID: 22765894]	Inhibition	7.48	pIC50
SU6656	Inhibition	7.14	pIC50
GSK-3 inhibitor XIII	Inhibition	7.09	pKi
NG-25	Inhibition	6.95	pIC50
SI306	Inhibition	6.89	pKi
compound 19a [PMID: 30503936]	Inhibition	6.62	pIC50
balamapimod	Inhibition	6.55	pIC50
compound 36 [PMID: 21958547]	Inhibition	6.53	pIC50
TAK-020	Inhibition	6.2	pIC50
compound 25 [PMID: 31260299]	Inhibition	6.04	pIC50

Binding affinities (BindingDB)

1739 measured of 2258 human assays (2413 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[(4-chloro-5-methoxy-2-methylphenyl)amino]-7-methoxy-8-[2-(morpholin-4-yl)ethoxy]benzo[g]quinoline-3-carbonitrile	IC50	0.15 nM
7-methoxy-8-[2-(morpholin-4-yl)ethoxy]-4-[(3,4,5-trimethoxyphenyl)amino]benzo[g]quinoline-3-carbonitrile	IC50	0.22 nM
Inhibitor 3	IC50	0.25 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-methoxy-8-[2-(4-methylpiperazin-1-yl)ethoxy]benzo[g]quinoline-3-carbonitrile	IC50	0.29 nM
4-[(4-chloro-5-methoxy-2-methylphenyl)amino]-7-methoxy-8-[2-(4-methylpiperazin-1-yl)ethoxy]benzo[g]quinoline-3-carbonitrile	IC50	0.31 nM
4-[(2-chloro-5-methoxy-4-methylphenyl)amino]-7-methoxy-8-[2-(morpholin-4-yl)ethoxy]benzo[g]quinoline-3-carbonitrile	IC50	0.33 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
CGP77675	IC50	0.4 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-methoxy-8-[2-(morpholin-4-yl)ethoxy]benzo[g]quinoline-3-carbonitrile	IC50	0.46 nM
4-[(2-chloro-4-fluoro-5-methoxyphenyl)amino]-7-methoxy-8-[2-(morpholin-4-yl)ethoxy]benzo[g]quinoline-3-carbonitrile	IC50	0.48 nM
4-[[7-(6-chloro-2-fluoro-3-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]-N-methyl-N-(2-pyrrolidin-1-ylethyl)benzamide	IC50	0.542 nM	US-8481536: Benzotriazine inhibitors of kinases
4-[(2-chloro-5-methoxy-4-methylphenyl)amino]-8-[2-(4-hydroxypiperidin-1-yl)ethoxy]-7-methoxybenzo[g]quinoline-3-carbonitrile	IC50	0.55 nM
4-[(E)-2-{3-cyano-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxyquinolin-7-yl}ethenyl]-1-oxidopyridin-1-ium	IC50	0.6 nM
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-[3-(4-hydroxypiperidin-1-yl)propoxy]-6-methoxy-3-quinolinecarbonitrile	IC50	0.64 nM
7-methoxy-8-[2-(4-methylpiperazin-1-yl)ethoxy]-4-[(3,4,5-trimethoxyphenyl)amino]benzo[g]quinoline-3-carbonitrile	IC50	0.69 nM
4-[[7-(6-chloro-2-fluoro-3-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide	IC50	0.7 nM	US-8481536: Benzotriazine inhibitors of kinases
4-[(2,4-dichloro-5-methoxyphenyl)amino]-8-[2-(4-hydroxypiperidin-1-yl)ethoxy]-7-methoxybenzo[g]quinoline-3-carbonitrile	IC50	0.72 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-{5-[(dimethylamino)methyl]furan-3-yl}-6-methoxyquinoline-3-carbonitrile	IC50	0.75 nM
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy}-3-quinolinecarbonitrile	IC50	0.76 nM
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-[3-(4-ethyl-1-piperazinyl)propoxy]-6-methoxy-3-quinolinecarbonitrile	IC50	0.77 nM
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-{5-[(4-methylpiperazin-1-yl)methyl]-3-furyl}-3-quinolinecarbonitrile	IC50	0.78 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinoline-3-carbonitrile	IC50	0.8 nM
IBRUTINIB	IC50	0.8 nM	US-9278100: Inhibitors of bruton’s tyrosine kinase for the treatment of solid tumors
4-[(2-bromo-4-chloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinoline-3-carbonitrile	IC50	0.95 nM
4-[[7-(5-hydroxy-2-methylphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide	IC50	0.955 nM	US-8481536: Benzotriazine inhibitors of kinases
N-[3-[2-[4-(2-hydroxyethylcarbamoyl)anilino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-4-methylphenyl]-3-(trifluoromethyl)benzamide	IC50	1 nM	US-8962637: Bicyclic compounds and their uses as dual c-SRC/JAK inhibitors
N-[4-methyl-3-[2-[4-(2-pyrrolidin-1-ylethoxy)anilino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]phenyl]piperidine-1-carboxamide	IC50	1 nM	US-8962637: Bicyclic compounds and their uses as dual c-SRC/JAK inhibitors
2-cyclopentyl-N-[4-methyl-3-[2-[4-(2-pyrrolidin-1-ylethoxy)anilino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]phenyl]acetamide	IC50	1 nM	US-8962637: Bicyclic compounds and their uses as dual c-SRC/JAK inhibitors
4-chloro-2-fluoro-3-[5-methyl-3-[4-(3-pyrrolidin-1-ylpropylsulfonyl)anilino]-1,2,4-benzotriazin-7-yl]phenol	IC50	1 nM	US-8481536: Benzotriazine inhibitors of kinases
4-[(2-Chloro-5-methoxy-4-methylphenyl)amino]-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarbonitrile	IC50	1.1 nM
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-propyl-1-piperazinyl)propoxy]-3-quinolinecarbonitrile	IC50	1.1 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(piperazin-1-yl)propoxy]quinoline-3-carbonitrile	IC50	1.1 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-8-methoxy-7-[2-(4-methylpiperazin-1-yl)ethoxy]benzo[g]quinoline-3-carbonitrile	IC50	1.1 nM
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
2,4-dichloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	IC50	1.1 nM	US-8481536: Benzotriazine inhibitors of kinases
4-[(4-Chloro-5-methoxy-2-methylphenyl)amino]-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarbonitrile	IC50	1.2 nM
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-piperidin-1-yl )propoxy]-3-quinolinecarbonitrile	IC50	1.2 nM
[4-[[7-(2-chloro-5-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]phenyl]-piperazin-1-ylmethanone	IC50	1.2 nM	US-8481536: Benzotriazine inhibitors of kinases
8-methoxy-7-[2-(morpholin-4-yl)ethoxy]-4-[(3,4,5-trimethoxyphenyl)amino]benzo[g]quinoline-3-carbonitrile	IC50	1.2 nM
4-chloro-3-[6-chloro-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	IC50	1.2 nM	US-8481536: Benzotriazine inhibitors of kinases
4-[[7-(6-chloro-2-fluoro-3-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]-N-methyl-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide	IC50	1.2 nM	US-8481536: Benzotriazine inhibitors of kinases
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[4-(4-morpholinyl)butoxy]-3-quinolinecarbonitrile	IC50	1.3 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-{3-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]propoxy}quinoline-3-carbonitrile	IC50	1.4 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1,4-diazepan-1-yl)propoxy]quinoline-3-carbonitrile	IC50	1.4 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(1-methylpiperidin-4-yl)propoxy]quinoline-3-carbonitrile	IC50	1.4 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-{5-[(4-hydroxypiperidin-1-yl)methyl]thiophen-3-yl}quinoline-3-carbonitrile	IC50	1.4 nM
4-[(4-chloro-5-methoxy-2-methylphenyl)amino]-7,8-dimethoxybenzo[g]quinoline-3-carbonitrile	IC50	1.4 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[5-(morpholin-4-ylmethyl)furan-3-yl]quinoline-3-carbonitrile	IC50	1.5 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-(2-methoxyethoxy)quinoline-3-carbonitrile	IC50	1.5 nM
4-[(4-chloro-5-methoxy-2-methylphenyl)amino]-8-methoxy-7-[2-(4-methylpiperazin-1-yl)ethoxy]benzo[g]quinoline-3-carbonitrile	IC50	1.5 nM

ChEMBL bioactivities

5079 potent at pChembl≥5 of 5572 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.80	Ki	0.016	nM	DASATINIB
10.52	IC50	0.03	nM	DASATINIB
9.92	IC50	0.12	nM	ELZOVANTINIB
9.92	IC50	0.12	nM	CHEMBL1241676
9.82	IC50	0.15	nM	CHEMBL196797
9.74	IC50	0.18	nM	CHEMBL3976548
9.70	IC50	0.2	nM	CHEMBL281957
9.70	IC50	0.2	nM	CHEMBL3216659
9.68	Kd	0.21	nM	DASATINIB
9.68	IC50	0.21	nM	DASATINIB
9.66	IC50	0.22	nM	CHEMBL425389
9.60	IC50	0.25	nM	CHEMBL78455
9.58	Ki	0.261	nM	CHEMBL4474070
9.54	IC50	0.29	nM	CHEMBL198650
9.53	Ki	0.295	nM	DASATINIB
9.52	IC50	0.3	nM	DASATINIB
9.52	IC50	0.3	nM	CHEMBL421024
9.51	IC50	0.31	nM	CHEMBL196889
9.50	IC50	0.3162	nM	CHEMBL516062
9.50	IC50	0.3162	nM	CHEMBL474998
9.48	IC50	0.33	nM	CHEMBL370633
9.40	IC50	0.4	nM	DASATINIB
9.37	IC50	0.43	nM	CHEMBL3984621
9.35	IC50	0.45	nM	CHEMBL1089405
9.35	Ki	0.449	nM	CHEMBL4538000
9.34	IC50	0.46	nM	CHEMBL195029
9.32	IC50	0.48	nM	CHEMBL198868
9.30	IC50	0.5	nM	DASATINIB
9.30	IC50	0.5	nM	CHEMBL364623
9.27	IC50	0.542	nM	CHEMBL3639501
9.26	IC50	0.55	nM	CHEMBL436486
9.26	IC50	0.55	nM	CHEMBL1242568
9.22	IC50	0.6	nM	CHEMBL178787
9.22	IC50	0.6	nM	CHEMBL3823104
9.22	IC50	0.6	nM	DASATINIB
9.22	IC50	0.6	nM	CHEMBL591325
9.21	IC50	0.61	nM	CHEMBL495306
9.19	IC50	0.64	nM	CHEMBL424262
9.16	IC50	0.69	nM	CHEMBL197713
9.15	IC50	0.7	nM	CHEMBL250821
9.15	IC50	0.7	nM	CHEMBL6149340
9.15	Kd	0.71	nM	CHEMBL386051
9.14	IC50	0.72	nM	CHEMBL197744
9.12	IC50	0.75	nM	CHEMBL219964
9.12	IC50	0.76	nM	CHEMBL338194
9.11	IC50	0.78	nM	CHEMBL219557
9.11	Ki	0.785	nM	CHEMBL4469856
9.11	IC50	0.77	nM	CHEMBL130529
9.10	IC50	0.8	nM	CHEMBL3695571
9.10	Ki	0.8	nM	CHEMBL3824089

PubChem BioAssay actives

2263 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	1893830: Binding affinity to Src (unknown origin) assessed as inhibition constant	ki	<0.0001	uM
(11S)-16-amino-2-ethyl-6-fluoro-11-methyl-14-oxo-10-oxa-2,13,17,18,21-pentazatetracyclo[13.5.2.04,9.018,22]docosa-1(21),4(9),5,7,15(22),16,19-heptaene-5-carbonitrile	2003537: Inhibition of SRC (unknown origin)	ic50	0.0001	uM
5-(4-amino-1-cyclopentylpyrazolo[3,4-d]pyrimidin-3-yl)-2-chlorophenol	507081: Inhibition of recombinant c-Src by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0001	uM
[5-amino-1-(2-chloro-5-hydroxyphenyl)pyrazol-4-yl]-(1H-indol-2-yl)methanone	1322599: Inhibition of human SRC by time-resolved fluorescence or time-resolved fluorescence assay	ic50	0.0002	uM
6-bromo-3-[(3E)-3-(2-piperazin-1-ylethoxyimino)indol-2-yl]-1H-indol-2-ol;dihydrochloride	1993951: Inhibition of recombinant GST-tagged c-Src catalytic domain (unknown origin) using pEY (4:1) as substrate incubated for 120 mins in presence of 33P-labeled ATP	ic50	0.0002	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-morpholin-4-ylpurin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0002	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-(4-methylpiperazin-1-yl)purin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0002	uM
[[4-[[6-(2,6-dichlorophenyl)-8-[3-(dimethylamino)propyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]phenyl]-hydroxyphosphoryl]methylphosphonic acid	205332: Inhibition of Src protein tyrosine kinase	ic50	0.0003	uM
2-[[6-[4-[2-[2-(2-aminoethoxy)ethoxy]ethyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide	1515651: Binding affinity to wild-type human partial length SRC (L240 to L536 residues) expressed in bacterial expression system by TR-FRET assay	ki	0.0003	uM
3-[4-amino-7-[4-[2-(2-hydroxyethylamino)ethoxy]phenyl]pyrrolo[2,3-d]pyrimidin-5-yl]phenol	352998: Inhibition of c-Src	ic50	0.0003	uM
3-[4-amino-7-[2-[2-(dimethylamino)ethyl]phenyl]pyrrolo[2,3-d]pyrimidin-5-yl]phenol	352998: Inhibition of c-Src	ic50	0.0003	uM
N-(2-chloro-6-methylphenyl)-2-[(2-methyl-6-piperazin-1-ylpyrimidin-4-yl)amino]-1,3-thiazole-5-carboxamide	1515651: Binding affinity to wild-type human partial length SRC (L240 to L536 residues) expressed in bacterial expression system by TR-FRET assay	ki	0.0004	uM
[5-amino-1-(2-chloro-5-hydroxyphenyl)pyrazol-4-yl]-[5-(morpholin-4-ylmethyl)-1H-indol-2-yl]methanone	1322599: Inhibition of human SRC by time-resolved fluorescence or time-resolved fluorescence assay	ic50	0.0004	uM
tert-butyl N-[4-[4-amino-1-[2-[4-(dimethylamino)piperidin-1-yl]ethyl]pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl]carbamate	1224919: eCF506, a potent and selection SRC inhibitor	ic50	0.0005	uM
tert-butyl N-[4-[4-amino-1-[2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl]carbamate	1310131: Inhibition of C-terminal His-tagged full length human SRC expressed in insect cells preincubated for 20 mins using poly[Glu,Tyr]4:1 as substrate measured after 5 to 120 mins in presence of [gamma-33P]ATP by Kinome assay	ic50	0.0005	uM
3-[2-[(E)-[2-(6-bromo-2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxyethyl-methylamino]propane-1,2-diol	1459479: Inhibition of recombinant c-Src (unknown origin) after 120 mins in presence of [33P]ATP	ic50	0.0005	uM
N-(4-dimethylphosphorylphenyl)-9-[(E)-2-(5-methyl-1H-indazol-4-yl)ethenyl]purin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-imidazol-1-ylpurin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-methoxypurin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-propan-2-yloxypurin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-(2-methoxyethoxy)purin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-(1-methylpiperidin-4-yl)purin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-pyridin-3-yloxypurin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
3-[9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-6-(4-dimethylphosphorylanilino)purin-2-yl]propanenitrile	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
1-tert-butyl-3-(4-chlorophenyl)pyrazolo[3,4-d]pyrimidin-4-amine	1407821: Inhibition of Src (unknown origin) using Src-family kinase bisamide rhodamine 110 peptide substrate after 1 hr by fluorescence assay	ic50	0.0005	uM
tert-butyl N-[4-[4-amino-1-[2-(4-piperidin-1-ylpiperidin-1-yl)ethyl]pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl]carbamate	1310131: Inhibition of C-terminal His-tagged full length human SRC expressed in insect cells preincubated for 20 mins using poly[Glu,Tyr]4:1 as substrate measured after 5 to 120 mins in presence of [gamma-33P]ATP by Kinome assay	ic50	0.0006	uM
8-[2-(dimethylamino)ethoxy]-2-(4-phenoxyphenyl)-6,11-dihydro-5H-pyrazolo[5,1-b][1,3]benzodiazepine-1-carboxamide	452196: Inhibition of SRC	ic50	0.0006	uM
3-[2-[(E)-[2-(6-bromo-2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxyethyl-methylamino]propane-1,2-diol;hydrochloride	1459479: Inhibition of recombinant c-Src (unknown origin) after 120 mins in presence of [33P]ATP	ic50	0.0006	uM
5-(4-amino-1-cyclopentylpyrazolo[3,4-d]pyrimidin-3-yl)-2-fluorophenol	507081: Inhibition of recombinant c-Src by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0006	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625016: Binding constant for SRC kinase domain	kd	0.0007	uM
4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[5-[(4-methylpiperazin-1-yl)methyl]furan-3-yl]quinoline-3-carbonitrile	1796979: Homogeneous Time-resolved Fluorescence (HTRF) Assay from Article 10.1021/jm061031t: “Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles.”	ic50	0.0008	uM
4-(2,4-dichloro-5-methoxyanilino)-7-[5-[(dimethylamino)methyl]furan-3-yl]-6-methoxyquinoline-3-carbonitrile	1796979: Homogeneous Time-resolved Fluorescence (HTRF) Assay from Article 10.1021/jm061031t: “Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles.”	ic50	0.0008	uM
6-bromo-3-[(3E)-3-[2-[4-[2-(2-hydroxyethoxy)ethyl]piperazin-1-yl]ethoxyimino]indol-2-yl]-1H-indol-2-ol	1459479: Inhibition of recombinant c-Src (unknown origin) after 120 mins in presence of [33P]ATP	ic50	0.0008	uM
tert-butyl N-[2-[2-[2-[4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazin-1-yl]ethoxy]ethoxy]ethyl]carbamate	1515651: Binding affinity to wild-type human partial length SRC (L240 to L536 residues) expressed in bacterial expression system by TR-FRET assay	ki	0.0008	uM
Dasatinib	2193617: Inhibition of GST tagged Src (unknown origin) assessed as inhibition of phosphorylation using PTK biotinylated peptide substrate 2 as substrate preincubated for 5 mins followed by [gamma-32P]ATP addition	ic50	0.0008	uM
Vandetanib	1876282: Inhibition of SRC (unknown origin)	ic50	0.0008	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	627293: Inhibition of c-Src using biotinylated substrate preincubated for 15 mins before substrate addition measured after 30 mins by fluorescence microplate analysis	ic50	0.0008	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	1206214: Inhibition of human Src	ic50	0.0009	uM
2-[2-[2-[2-[4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazin-1-yl]ethoxy]ethoxy]ethylamino]-2-oxoethanesulfonic acid	1515651: Binding affinity to wild-type human partial length SRC (L240 to L536 residues) expressed in bacterial expression system by TR-FRET assay	ki	0.0009	uM
4-[2-[2-[2-[4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazin-1-yl]ethoxy]ethoxy]ethylcarbamoyl]cyclobutane-1,2,3-tricarboxylic acid	1515651: Binding affinity to wild-type human partial length SRC (L240 to L536 residues) expressed in bacterial expression system by TR-FRET assay	ki	0.0009	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-propan-2-ylpurin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0009	uM
N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine	360772: Inhibition of Src kinase	ic50	0.0010	uM
N-(2-chloro-6-methylphenyl)-2-[(2,6-dimethylpyrimidin-4-yl)amino]-1,3-thiazole-5-carboxamide	240660: Inhibitory activity against Src tyrosine kinase	ic50	0.0010	uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1425175: 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
methyl 2-[4-[4-amino-5-(3-hydroxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]piperidin-1-yl]acetate	224318: Inhibition of p60 c-Src tyrosine kinase enzyme activity in liquid-phase tyrosine phosphorylation assay at 830 ng/mL	ic50	0.0010	uM
(2,6-dimethylphenyl) N-[(2,5-dimethoxyphenyl)methyl]-N-[2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]carbamate	1797647: HTRF Kinase Inhibition Assay from Article 10.1021/jm060435i: “Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity.”	ic50	0.0010	uM
(2,6-dimethylphenyl) N-[2-[3,5-dimethoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]-N-(2,4-dimethoxyphenyl)carbamate	1797647: HTRF Kinase Inhibition Assay from Article 10.1021/jm060435i: “Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity.”	ic50	0.0010	uM
(2,6-dimethylphenyl) N-[2-[3,5-dimethoxy-4-[3-(4-methylpiperazin-1-yl)propoxy]anilino]pyrimidin-4-yl]-N-(2,4-dimethoxyphenyl)carbamate	1797647: HTRF Kinase Inhibition Assay from Article 10.1021/jm060435i: “Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity.”	ic50	0.0010	uM
(2,6-dimethylphenyl) N-[2-[3,5-dimethoxy-4-[2-(4-methylpiperazin-1-yl)ethoxy]anilino]pyrimidin-4-yl]-N-(2,4-dimethoxyphenyl)carbamate	1797647: HTRF Kinase Inhibition Assay from Article 10.1021/jm060435i: “Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity.”	ic50	0.0010	uM
3-[2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)ethynyl]-N-[3-bromo-4-[(4-methylpiperazin-1-yl)methyl]phenyl]-4-methylbenzamide	1206214: Inhibition of human Src	ic50	0.0010	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
AG 1879	increases response to substance, increases phosphorylation, affects binding, increases activity, increases expression (+9 more)	25
Dasatinib	decreases activity, increases reaction, affects cotreatment, decreases phosphorylation, affects binding (+2 more)	12
Estradiol	decreases reaction, affects cotreatment, increases abundance, increases phosphorylation, increases expression (+4 more)	8
Resveratrol	increases phosphorylation, affects phosphorylation, affects cotreatment, affects binding, decreases phosphorylation (+6 more)	7
Benzo(a)pyrene	increases expression, increases methylation, increases phosphorylation, decreases reaction, increases reaction (+3 more)	7
bisphenol A	increases phosphorylation, affects binding, decreases expression, decreases activity, decreases reaction (+3 more)	6
sodium arsenite	affects cotreatment, affects reaction, increases activity, affects expression, increases expression (+4 more)	6
Tetrachlorodibenzodioxin	affects localization, affects cotreatment, increases activity, increases reaction, increases expression (+3 more)	6
Hexachlorobenzene	decreases reaction, decreases response to substance, affects localization, affects activity, affects phosphorylation (+4 more)	5
Zinc	increases expression, decreases activity, decreases reaction, increases phosphorylation	5
Arsenic Trioxide	decreases reaction, increases phosphorylation, affects cotreatment, decreases expression, increases response to substance (+1 more)	4
Arsenic	increases expression, increases phosphorylation, increases activity, increases reaction, increases abundance (+1 more)	4
Ozone	affects cotreatment, increases oxidation, increases expression, increases abundance, decreases expression (+1 more)	4
Valproic Acid	affects cotreatment, decreases expression, increases methylation	4
evodiamine	affects binding, decreases reaction, increases reaction, increases phosphorylation, decreases expression (+1 more)	3
4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine	decreases reaction, increases phosphorylation, affects binding, increases reaction, decreases phosphorylation	3
4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline	increases phosphorylation, increases abundance, decreases reaction	3
Acetylcysteine	increases phosphorylation, decreases phosphorylation, decreases reaction	3
Dihydrotestosterone	affects binding, increases reaction, increases activity, increases phosphorylation, decreases reaction (+1 more)	3
Aflatoxin B1	increases expression	3
Cadmium Chloride	increases reaction, affects reaction, decreases reaction, increases abundance, increases phosphorylation (+2 more)	3
methyleugenol	increases expression	2
perfluorooctanoic acid	affects expression, increases expression, affects cotreatment	2
ochratoxin A	decreases expression, increases phosphorylation	2
butylbenzyl phthalate	decreases expression, increases phosphorylation, decreases reaction	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases expression, increases abundance	2
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	affects cotreatment, decreases expression, decreases reaction, affects binding	2
RTKI cpd	decreases reaction, increases phosphorylation	2
CGP 77675	decreases activity, increases reaction, decreases phosphorylation, decreases reaction, increases phosphorylation (+3 more)	2
monomethylarsonous acid	increases phosphorylation, affects reaction, decreases activity, decreases reaction, increases expression	2

ChEMBL screening assays

1917 unique, capped per target: 1858 binding, 43 functional, 16 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL807847	Binding	Selectivity for Vascular endothelial growth factor receptor 2 over c-Src kinase	Synthesis and initial SAR studies of 3,6-disubstituted pyrazolo[1,5-a]pyrimidines: a new class of KDR kinase inhibitors. — Bioorg Med Chem Lett
CHEMBL845306	Functional	Selectivity for VEGF-receptor 2 (KDR) over c-Src	Design and synthesis of 1,5-diarylbenzimidazoles as inhibitors of the VEGF-receptor KDR. — Bioorg Med Chem Lett
CHEMBL4136609	ADMET	Inhibition of recombinant SRC (unknown origin) using polyE4Y as substrate by pyruvate kinase-lactate dehydrogenase coupled assay	Mtb PKNA/PKNB Dual Inhibition Provides Selectivity Advantages for Inhibitor Design To Minimize Host Kinase Interactions. — ACS Med Chem Lett

Cellosaurus cell lines

11 cell lines: 9 cancer cell line, 1 telomerase immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8Q5	Abcam HCT 116 SRC KO	Cancer cell line	Male
CVCL_B9BV	Abcam MCF-7 SRC KO	Cancer cell line	Female
CVCL_B9SL	Abcam A-549 SRC KO	Cancer cell line	Male
CVCL_C3KI	N/Tert-1 SRC	Telomerase immortalized cell line	Male
CVCL_D8BE	Ubigene A-549 SRC KO	Cancer cell line	Male
CVCL_D8W8	Ubigene HCT 116 SRC KO	Cancer cell line	Male
CVCL_D9T0	Ubigene HEK293 SRC KO	Transformed cell line	Female
CVCL_E0PY	Ubigene HeLa SRC KO	Cancer cell line	Female
CVCL_TQ36	HAP1 SRC (-) 1	Cancer cell line	Male
CVCL_TQ37	HAP1 SRC (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00114829	PHASE4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	PHASE4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	PHASE4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	PHASE4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	PHASE4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	PHASE4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	PHASE4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	PHASE4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	PHASE4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	PHASE4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	PHASE4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	PHASE4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	PHASE4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	PHASE4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	PHASE4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	PHASE4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	PHASE4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00868569	PHASE4	UNKNOWN	Transhepatic Arterial Chemotherapy (TAC) Versus Transcatheter Arterial Chemoembolization (TACE) Plus Folfox4 as the Treatment of Unresectable Liver Metastasis of Colorectal Cancer
NCT00868816	PHASE4	COMPLETED	Oxaliplatine Based Adjuvant Chemotherapy for Stage II/III Colorectal Cancer: 8 Cycles Versus 12 Cycles
NCT00874406	PHASE4	UNKNOWN	Preoperative Transhepatic Arterial Chemotherapy (TAC) in the Treatment of Liver Metastasis of Resectable Colorectal Cancer
NCT00928928	PHASE4	COMPLETED	Oxidative Stress Markers in Open and Laparoscopic Colectomy for Cancer
NCT00942461	PHASE4	COMPLETED	Inflammatory Response in Laparoscopic and Open Colectomy
NCT01023633	PHASE4	UNKNOWN	OPTIMOX1 in Chinese mCRC Patients
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01315990	PHASE4	UNKNOWN	FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
NCT01493713	PHASE4	COMPLETED	Correlation Between RECIST, Morphologic Response by CT- Histopathologic Response in Hepatic Metastasis Secondary to Colorectal Cancer
NCT01609660	PHASE4	COMPLETED	Impact of Probiotics on the Intestinal Microbiota
NCT01641458	PHASE4	COMPLETED	Pharmacology-driven Dosing of Fluoropyrimidines in Cancer Patients
NCT01689792	PHASE4	COMPLETED	A Multi-centre Study Comparing the Polyp Detection Rate of Two Different Types of Bowel Preparation: a 2-litre Solution (MOVIPREP®) Versus a Hyperosmotic and Stimulant Combined Low Volume Bowel Preparation (Sodium Picosulfate and Magnesium Citrate)
NCT01695772	PHASE4	COMPLETED	A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
NCT01695863	PHASE4	COMPLETED	Efficacy and Patient Satisfaction of Miralax and Gatorade Versus Movi Prep
NCT01706822	PHASE4	TERMINATED	Radial Reload Laparoscopic LAR Case Series
NCT01740947	PHASE4	TERMINATED	Does Administration of Antibiotics in Patients Undergoing Surgery for Colorectal Cancer Result in Less Complications and Better Prognosis?
NCT01831310	PHASE4	COMPLETED	Nutrition for Colorectal Cancer Patients and Neutrophil Functions
NCT01841294	PHASE4	UNKNOWN	NK Activity Modulation Induced by Intravenous Lidocaine During Colorectal Laparoscopic Surgery
NCT01959061	PHASE4	UNKNOWN	Efficacy and Safety of Raltitrexed-based Transarterial Chemoembolisation(TACE)for Colorectal Cancer Liver Metastases
NCT02032953	PHASE4	UNKNOWN	Enhancing the Anabolic Effect of Perioperative Nutrition With Insulin While Maintaining Normoglycemia
NCT02567331	PHASE4	COMPLETED	A Study of Capecitabine (Xeloda) in Patients With Metastatic Colorectal Cancer