YES1
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Also known as Yesc-yesHsT441
Summary
YES1 (YES proto-oncogene 1, Src family tyrosine kinase, HGNC:12841) is a protein-coding gene on chromosome 18p11.32, encoding Tyrosine-protein kinase Yes (P07947). Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation.
This gene is the cellular homolog of the Yamaguchi sarcoma virus oncogene. The encoded protein has tyrosine kinase activity and belongs to the src family of proteins. This gene lies in close proximity to thymidylate synthase gene on chromosome 18, and a corresponding pseudogene has been found on chromosome 22.
Source: NCBI Gene 7525 — RefSeq curated summary.
At a glance
- GWAS associations: 13
- Clinical variants (ClinVar): 73 total
- Druggable target: yes — 66 molecules with ChEMBL bioactivity
- MANE Select transcript:
NM_005433
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:12841 |
| Approved symbol | YES1 |
| Name | YES proto-oncogene 1, Src family tyrosine kinase |
| Location | 18p11.32 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | Yes, c-yes, HsT441 |
| Ensembl gene | ENSG00000176105 |
| Ensembl biotype | protein_coding |
| OMIM | 164880 |
| Entrez | 7525 |
Gene structure
Transcript identifiers
Ensembl transcripts: 24 — 22 protein_coding, 2 protein_coding_CDS_not_defined
ENST00000314574, ENST00000577611, ENST00000577961, ENST00000581960, ENST00000584307, ENST00000892684, ENST00000892685, ENST00000892686, ENST00000892687, ENST00000892688, ENST00000892689, ENST00000925072, ENST00000925073, ENST00000925074, ENST00000925075, ENST00000925076, ENST00000925077, ENST00000925078, ENST00000925079, ENST00000925080, ENST00000945836, ENST00000945837, ENST00000945838, ENST00000945839
RefSeq mRNA: 1 — MANE Select: NM_005433
NM_005433
CCDS: CCDS11824
Canonical transcript exons
ENST00000314574 — 12 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001214226 | 732834 | 732965 |
| ENSE00001214236 | 736808 | 736961 |
| ENSE00001214245 | 739735 | 739811 |
| ENSE00001214251 | 742918 | 743097 |
| ENSE00001214256 | 743260 | 743415 |
| ENSE00001214274 | 745948 | 746051 |
| ENSE00001214283 | 747920 | 748018 |
| ENSE00001214293 | 751705 | 751804 |
| ENSE00001542048 | 721588 | 724632 |
| ENSE00001665786 | 745708 | 745857 |
| ENSE00002704426 | 812114 | 812242 |
| ENSE00003596873 | 756557 | 756835 |
Expression profiles
Bgee: expression breadth ubiquitous, 295 present calls, max score 98.57.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.8243 / max 343.0358, expressed in 1669 samples.
FANTOM5 promoters (4 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 170952 | 29.6834 | 1659 |
| 170953 | 4.2716 | 1411 |
| 170954 | 0.5509 | 267 |
| 170955 | 0.3185 | 146 |
Top tissues by expression
298 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| secondary oocyte | CL:0000655 | 98.57 | gold quality |
| oocyte | CL:0000023 | 98.42 | gold quality |
| jejunal mucosa | UBERON:0000399 | 97.17 | gold quality |
| parotid gland | UBERON:0001831 | 96.75 | gold quality |
| buccal mucosa cell | CL:0002336 | 96.73 | gold quality |
| visceral pleura | UBERON:0002401 | 96.55 | gold quality |
| gingival epithelium | UBERON:0001949 | 96.47 | gold quality |
| esophagus squamous epithelium | UBERON:0006920 | 96.43 | gold quality |
| parietal pleura | UBERON:0002400 | 96.18 | gold quality |
| pleura | UBERON:0000977 | 96.12 | gold quality |
| endothelial cell | CL:0000115 | 96.09 | gold quality |
| gingiva | UBERON:0001828 | 96.01 | gold quality |
| squamous epithelium | UBERON:0006914 | 96.00 | gold quality |
| corpus epididymis | UBERON:0004359 | 95.69 | gold quality |
| mammary duct | UBERON:0001765 | 95.46 | gold quality |
| oral cavity | UBERON:0000167 | 95.37 | gold quality |
| skin of hip | UBERON:0001554 | 95.26 | gold quality |
| epithelium of mammary gland | UBERON:0003244 | 95.24 | gold quality |
| lower lobe of lung | UBERON:0008949 | 95.24 | gold quality |
| nephron tubule | UBERON:0001231 | 95.18 | gold quality |
| mucosa of sigmoid colon | UBERON:0004993 | 95.12 | gold quality |
| choroid plexus epithelium | UBERON:0003911 | 95.03 | gold quality |
| amniotic fluid | UBERON:0000173 | 94.91 | gold quality |
| tibia | UBERON:0000979 | 94.74 | gold quality |
| epithelium of esophagus | UBERON:0001976 | 94.71 | gold quality |
| renal glomerulus | UBERON:0000074 | 94.70 | gold quality |
| cartilage tissue | UBERON:0002418 | 94.65 | gold quality |
| colonic mucosa | UBERON:0000317 | 94.54 | gold quality |
| periodontal ligament | UBERON:0008266 | 94.50 | gold quality |
| metanephric glomerulus | UBERON:0004736 | 94.48 | gold quality |
Single-cell (SCXA)
Detected in 3 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 9.16 |
| E-MTAB-7381 | no | 58.50 |
| E-CURD-112 | no | 3.30 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): EGR1, NANOG
miRNA regulators (miRDB)
190 targeting YES1, 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-340-5P | 100.00 | 72.50 | 4437 |
| HSA-MIR-3163 | 100.00 | 77.23 | 8605 |
| HSA-MIR-30A-5P | 100.00 | 76.31 | 3233 |
| HSA-MIR-30B-5P | 100.00 | 76.29 | 3248 |
| HSA-MIR-30C-5P | 100.00 | 76.29 | 3248 |
| HSA-MIR-30D-5P | 100.00 | 76.32 | 3233 |
| HSA-MIR-30E-5P | 100.00 | 76.32 | 3242 |
| HSA-MIR-548C-3P | 99.99 | 74.01 | 7587 |
| HSA-MIR-3662 | 99.99 | 73.82 | 5684 |
| HSA-MIR-371B-5P | 99.99 | 75.34 | 4759 |
| HSA-MIR-5696 | 99.98 | 72.36 | 4487 |
| HSA-MIR-4775 | 99.98 | 75.00 | 6394 |
| HSA-MIR-12136 | 99.98 | 72.81 | 5713 |
| HSA-MIR-520D-5P | 99.98 | 73.34 | 4883 |
| HSA-MIR-524-5P | 99.98 | 73.43 | 4882 |
| HSA-MIR-548P | 99.98 | 72.25 | 3784 |
| 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-607 | 99.97 | 73.62 | 5593 |
| HSA-MIR-507 | 99.97 | 70.11 | 1915 |
| HSA-MIR-2110 | 99.96 | 66.68 | 1930 |
| HSA-MIR-548AJ-3P | 99.96 | 73.38 | 5345 |
| HSA-MIR-548X-3P | 99.96 | 73.38 | 5345 |
| HSA-MIR-146A-5P | 99.96 | 68.93 | 988 |
| HSA-MIR-146B-5P | 99.96 | 69.13 | 977 |
| HSA-MIR-4666A-3P | 99.96 | 71.71 | 3434 |
| HSA-MIR-570-3P | 99.96 | 72.41 | 4910 |
| HSA-MIR-590-3P | 99.96 | 74.34 | 6478 |
Literature-anchored findings (GeneRIF, showing 40)
- cAMP activates while Ca(2+) inhibits human sperm c-yes kinase activity (PMID:12080032)
- QM binds to c-yes at the SH3 domain in tumor cell lines (PMID:12138090)
- This review summarizes the potential functions of c-Yes and its ability to modulate signals that are distinct from c-Src. (PMID:12456296)
- Src family kinase Yes triggers hyperosmotic activation of the epidermal growth factor receptor and CD95 (PMID:15039424)
- activation of c-Yes is important for maintaining embryonic stem cells in an undifferentiated state (PMID:15148312)
- c-Yes 3’-UTR contains at least three newly identified adenine/uridine-rich elements (AREs) which are bound specifically by ARE-binding proteins HuR and AUF1. (PMID:16289864)
- Vascular endothelial growth factor (VEGF)-induced cell migration is significantly decreased in Yes-deficient retinal microvascular endothelial cells. (PMID:16400523)
- NFAT1, a transcription factor connected with breast cancer metastasis, is activated by Wnt-5a through a Ca2+ signaling pathway in human breast epithelial cells which was simultaneously counteracted by a Wnt-5a-induced Yes/Cdc42 signaling pathway. (PMID:16880514)
- activation of the protooncogene product c-Yes may play a significant role in the malignant transformation of hepatocytes (PMID:17007035)
- The results were confirmed at the level of mRNA and protein, and suggested that four genes (OPCML, RNASE1, YES1 and ACK1) could play a key role in the tumorigenesis and metastasis of gastric cancer. (PMID:17109515)
- Nucleus-located c-Yes may be a useful marker to detect early-stage hepatocellular carcinoma. (PMID:17143518)
- Amyloid aggregation by an SH3 domain from the Src family. (PMID:17418139)
- Thus, these results suggest that endogenous c-Src, c-Yes, and Lyn are differentially activated through Cdc2 activation during M phase. (PMID:17692281)
- c-Yes induction results in increased colorectal carcinoma cell motility but did not promote proliferation. In later stages of colorectal carcinogenesis, elevations in c-Yes levels/activity may promote cancer spread & metastasis rather than tumor growth. (PMID:17898870)
- Binding of CD95 Ligand to CD95 on glioblastoma cells recruit Yes and the p85 subunit of phosphatidylinositol 3-kinase to CD95, which signal invasion via the glycogen synthase kinase 3-beta pathway and subsequent expression of matrix metalloproteinases. (PMID:18328427)
- These results suggest that SFK trafficking is specified by the palmitoylation state in the SH4 domain. (PMID:19258394)
- Cloning of the complete coding sequence of the cDNA of the Csk and Yes tyrosine kinases genes of the human lymphocytes and retina have been carried out. (PMID:19757166)
- Data show that found that IFIH1, a susceptibility gene of type 1 diabetes, interacts with YES1, which plays a role in glucose transport. (PMID:19797678)
- Study identified the previously reported pathogenic mutation of NTRK3 in a KRAS/BRAF wild-type tumor and 2 somatic mutations in the Src family of kinases (YES1 and LYN) that would be expected to cause structural changes. (PMID:19893451)
- Both YES and STAT1 were verified as direct miR-145 targets (PMID:20098684)
- c-Yes was expressed in malignant melanoma, and squamous cell carcinoma type skin neoplasms. (PMID:20796316)
- Yes-associated protein may play important roles in different pathways in distinct lung tumor subtypes. (PMID:21190720)
- c-Yes regulates specific oncogenic signalling pathways important for colon cancer progression that is not shared with c-Src. (PMID:21390316)
- Functional activation of Src family kinase yes protein is essential for the enhanced malignant properties of human melanoma cells expressing ganglioside GD3. (PMID:21454696)
- Taken together, our findings demonstrate that Yes and Lyn phosphorylate EGFR at Y1101, which influences EGFR nuclear translocation in this model of cetuximab resistance. (PMID:22430206)
- study concludes that Yes is a central mediator for malignant mesothelioma cell growth that is not shared with other Src family kinases such as c-Src (PMID:22948717)
- we identified CRKL/YES as critical interrelated pathways necessary for rhabdomyosarcoma cell growth and survival and suggest a potential therapeutic role of SRC family kinase inhibition in the treatment of rhabdomyosarcoma. (PMID:23318429)
- Expression of HPV type 16 E7 resulted in increase in Src and Yes proteins level, but did not alter the level of Fyn. (PMID:23497302)
- YES1 and YAP transcript levels were higher in liver metastases of patients with colon cancer after 5FU-based neoadjuvant chemotherapy. (PMID:24323901)
- YES kinase as a proximal glucose-specific signal in the Cdc42-signaling cascade. (PMID:24610809)
- Results demonstrate a unique role for Yes in phosphorylation of FAK and in promoting PCa metastasis. Therefore, phosphorylated FAK Y861 and increased Yes expression may be predictive markers for PCa metastasis. (PMID:25868388)
- findings indicate that miR-203 induces the apoptosis of KB cells by directly targeting Yes-1, suggesting its application in anti-cancer therapeutics (PMID:25910964)
- Increased YES/SFK activation might serve as a clinical biomarker for predicting tumor resistance to IGF-1R inhibition. (PMID:25925378)
- Up-regulation of miR-210 inhibits hepatocellular carcinoma cell proliferation. Yes1 is a target of miR-210 and affects cell proliferation in HCC. (PMID:26676187)
- Our results suggest that H19 functions as a competitive endogenous RNA (ceRNA) by acting as a sink for miR-17-5p, revealing a potential ceRNA regulatory network involving H19 and miR-17-5p with a role in the modulation of YES1 expression (PMID:27093644)
- c-Yes plays an important role in migration and invasion of epithelial ovarian cancer. (PMID:27289010)
- Study on the role of miR-140-5p in inhibiting tumorigenesis in gastric cancer thru targeting YES proto-oncogene 1(YES1). (PMID:28818100)
- The downregulation of miR-199a contributes to paclitaxel (PTX) resistance in prostate cancer. YES1 mediates the regulation of miR-199a in prostate cancer PTX resistance. (PMID:29204706)
- findings identify acquired amplification of YES1 as a recurrent and targetable mechanism of resistance to EGFR inhibition in EGFR-mutant lung cancers and demonstrate the utility of transposon mutagenesis in discovering clinically relevant mechanisms of drug resistance. (PMID:29875142)
- YES1 is essential for NSCLC carcinogenesis. YES1 overexpression induced metastatic spread in preclinical in vivo models. YES1 genetic depletion by CRISPR/Cas9 technology significantly reduced tumor growth and metastasis. (PMID:31166114)
Cross-species orthologs
3 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | yes1 | ENSDARG00000005941 |
| mus_musculus | Yes1 | ENSMUSG00000014932 |
| rattus_norvegicus | Yes1 | ENSRNOG00000037227 |
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), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)
Protein
Protein identifiers
Tyrosine-protein kinase Yes — P07947 (reviewed: P07947)
Alternative names: Proto-oncogene c-Yes, p61-Yes
All UniProt accessions (2): P07947, J3QRU1
UniProt curated annotations — full annotation on UniProt →
Function. Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by receptor tyrosine kinases (RTKs) including EGFR, PDGFR, CSF1R and FGFR leads to recruitment of YES1 to the phosphorylated receptor, and activation and phosphorylation of downstream substrates. Upon EGFR activation, promotes the phosphorylation of PARD3 to favor epithelial tight junction assembly. Participates in the phosphorylation of specific junctional components such as CTNND1 by stimulating the FYN and FER tyrosine kinases at cell-cell contacts. Upon T-cell stimulation by CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and induces T-cell migration. Participates in CD95L/FASLG signaling pathway and mediates AKT-mediated cell migration. Plays a role in cell cycle progression by phosphorylating the cyclin-dependent kinase 4/CDK4 thus regulating the G1 phase. Also involved in G2/M progression and cytokinesis. Catalyzes phosphorylation of organic cation transporter OCT2 which induces its transport activity.
Subunit / interactions. Interacts with YAP1 and CSF1R. Interacts with CTNND1; this interaction allows YES1-mediated activation of FYN and FER and subsequent phosphorylation of CTNND1. Interacts with FASLG. Interacts with IL6ST/gp130. Interacts with SCRIB, when YES1 is in a closed conformation; the interaction facilitates YES1 autophosphorylation.
Subcellular location. Cell membrane. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Cytosol. Cell junction.
Tissue specificity. Expressed in the epithelial cells of renal proximal tubules and stomach as well as hematopoietic cells in the bone marrow and spleen in the fetal tissues. In adult, expressed in epithelial cells of the renal proximal tubules and present in keratinocytes in the basal epidermal layer of epidermis.
Post-translational modifications. Phosphorylated. Phosphorylation by CSK on the C-terminal tail maintains the enzyme in an inactive state. Autophosphorylation at Tyr-426 maintains enzyme activity by blocking CSK-mediated inhibition. Palmitoylation at Cys-3 promotes membrane localization.
Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.
RefSeq proteins (1): NP_005424* (*=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 |
| IPR035751 | Yes_SH3 | 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 (30 total): modified residue 8, strand 5, domain 3, lipid moiety-binding region 2, sequence variant 2, binding site 2, initiator methionine 1, chain 1, mutagenesis site 1, turn 1, helix 1, region of interest 1, compositionally biased region 1, active site 1
Structure
Experimental structures (PDB)
1 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 2HDA | X-RAY DIFFRACTION | 1.9 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P07947-F1 | 83.19 | 0.67 |
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): 396 (proton acceptor)
Ligand- & substrate-binding residues (2): 283–291; 305
Post-translational modifications (10): 21, 32, 40, 336, 345, 426, 446, 537, 2, 3
Mutagenesis-validated functional residues (1):
| Position | Phenotype |
|---|---|
| 426 | about 50% loss of csk-mediated inhibition. |
Function
Pathways and Gene Ontology
Reactome pathways
17 pathways
| ID | Pathway |
|---|---|
| R-HSA-1227986 | Signaling by ERBB2 |
| R-HSA-1433557 | Signaling by SCF-KIT |
| R-HSA-1433559 | Regulation of KIT signaling |
| R-HSA-2029481 | FCGR activation |
| R-HSA-210990 | PECAM1 interactions |
| R-HSA-2682334 | EPH-Ephrin signaling |
| R-HSA-389356 | Co-stimulation by CD28 |
| R-HSA-389513 | Co-inhibition by CTLA4 |
| R-HSA-3928662 | EPHB-mediated forward signaling |
| R-HSA-3928663 | EPHA-mediated growth cone collapse |
| R-HSA-3928665 | EPH-ephrin mediated repulsion of cells |
| R-HSA-8940973 | RUNX2 regulates osteoblast differentiation |
| R-HSA-912631 | Regulation of signaling by CBL |
| R-HSA-9664323 | FCGR3A-mediated IL10 synthesis |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells |
MSigDB gene sets: 388 (showing top):
GGGACCA_MIR133A_MIR133B, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CARBOHYDRATE_TRANSPORT, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, DORSAM_HOXA9_TARGETS_UP, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, TGCACTT_MIR519C_MIR519B_MIR519A, HOFMANN_CELL_LYMPHOMA_UP, PID_NETRIN_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN
GO Biological Process (15): negative regulation of inflammatory response to antigenic stimulus (GO:0002862), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), regulation of D-glucose transmembrane transport (GO:0010827), cell differentiation (GO:0030154), T cell costimulation (GO:0031295), cellular response to platelet-derived growth factor stimulus (GO:0036120), protein modification process (GO:0036211), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), regulation of vascular permeability (GO:0043114), positive regulation of transcription by RNA polymerase II (GO:0045944), ephrin receptor signaling pathway (GO:0048013), leukocyte migration (GO:0050900), cellular response to retinoic acid (GO:0071300), cellular response to transforming growth factor beta stimulus (GO:0071560), protein phosphorylation (GO:0006468)
GO Molecular Function (12): phosphotyrosine residue binding (GO:0001784), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), signaling receptor binding (GO:0005102), ATP binding (GO:0005524), enzyme binding (GO:0019899), transmembrane transporter binding (GO:0044325), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)
GO Cellular Component (11): Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829), actin filament (GO:0005884), plasma membrane (GO:0005886), focal adhesion (GO:0005925), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020), anchoring junction (GO:0070161)
Reactome top-level categories
Rollup of top-13 pathways:
| Category | Pathways |
|---|---|
| EPH-Ephrin signaling | 3 |
| Signaling by Receptor Tyrosine Kinases | 2 |
| Regulation of T cell activation by CD28 family | 2 |
| Signaling by SCF-KIT | 1 |
| Fcgamma receptor (FCGR) dependent phagocytosis | 1 |
| Cell surface interactions at the vascular wall | 1 |
| Axon guidance | 1 |
| RUNX2 regulates bone development | 1 |
| Interleukin-3, Interleukin-5 and GM-CSF signaling | 1 |
| Anti-inflammatory response favouring Leishmania parasite infection | 1 |
| Leishmania phagocytosis | 1 |
| Signaling by KIT in disease | 1 |
| Cytokine Signaling in Immune system | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| protein binding | 3 |
| cellular anatomical structure | 3 |
| cellular response to growth factor stimulus | 2 |
| cytoplasm | 2 |
| 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 |
| enzyme-linked receptor protein signaling pathway | 1 |
| regulation of transmembrane transport | 1 |
| D-glucose transmembrane transport | 1 |
| cellular developmental process | 1 |
| lymphocyte costimulation | 1 |
| positive regulation of T cell activation | 1 |
| response to platelet-derived growth factor | 1 |
| protein metabolic process | 1 |
| macromolecule modification | 1 |
| Fc receptor mediated stimulatory signaling pathway | 1 |
| phagocytosis | 1 |
| Fc-gamma receptor signaling pathway | 1 |
| vascular process in circulatory system | 1 |
| blood circulation | 1 |
| regulation of biological quality | 1 |
| regulation of transcription by RNA polymerase II | 1 |
| transcription by RNA polymerase II | 1 |
| positive regulation of DNA-templated transcription | 1 |
| cell surface receptor protein tyrosine kinase signaling pathway | 1 |
| immune system process | 1 |
| cell migration | 1 |
| response to retinoic acid | 1 |
| cellular response to lipid | 1 |
| cellular response to oxygen-containing compound | 1 |
| response to transforming growth factor beta | 1 |
| phosphorylation | 1 |
| protein modification process | 1 |
| protein phosphorylated amino acid binding | 1 |
| protein kinase activity | 1 |
| protein tyrosine kinase activity | 1 |
| adenyl ribonucleotide binding | 1 |
| purine ribonucleoside triphosphate binding | 1 |
Protein interactions and networks
STRING
2582 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| YES1 | YAP1 | P46937 | 936 |
| YES1 | TBX5 | Q99593 | 756 |
| YES1 | TYMS | P04818 | 752 |
| YES1 | ADRA2C | P18825 | 691 |
| YES1 | EGFR | P00533 | 612 |
| YES1 | CTNNB1 | P35222 | 566 |
| YES1 | GRB2 | P29354 | 562 |
| YES1 | OCLN | Q16625 | 543 |
| YES1 | TJP1 | Q07157 | 527 |
| YES1 | SHC1 | P29353 | 509 |
| YES1 | CDC42 | P21181 | 501 |
| YES1 | CAV1 | Q03135 | 482 |
| YES1 | PTPN13 | Q12923 | 475 |
| YES1 | MAP2K1 | Q02750 | 456 |
| YES1 | MAP2K2 | P36507 | 447 |
IntAct
447 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| YES1 | SOCS3 | psi-mi:“MI:0915”(physical association) | 0.720 |
| PTK2 | YES1 | psi-mi:“MI:0915”(physical association) | 0.720 |
| YES1 | FXR2 | psi-mi:“MI:0915”(physical association) | 0.720 |
| YES1 | TRAF2 | psi-mi:“MI:0915”(physical association) | 0.720 |
| YES1 | ZBTB8A | psi-mi:“MI:0915”(physical association) | 0.720 |
| YES1 | SSBP3 | psi-mi:“MI:0915”(physical association) | 0.720 |
| YES1 | THAP1 | psi-mi:“MI:0915”(physical association) | 0.720 |
| YES1 | TRAF6 | psi-mi:“MI:0915”(physical association) | 0.720 |
| SSBP3 | YES1 | psi-mi:“MI:0915”(physical association) | 0.720 |
| TRAF6 | YES1 | psi-mi:“MI:0915”(physical association) | 0.720 |
| SOCS3 | YES1 | psi-mi:“MI:0915”(physical association) | 0.720 |
| THAP1 | YES1 | psi-mi:“MI:0915”(physical association) | 0.720 |
BioGRID (513): SPRR2A (Reconstituted Complex), YES1 (Two-hybrid), YES1 (Two-hybrid), YES1 (Two-hybrid), SOCS3 (Two-hybrid), FXR2 (Two-hybrid), SSBP3 (Two-hybrid), THAP1 (Two-hybrid), NIF3L1 (Two-hybrid), C1orf94 (Two-hybrid), FUNDC1 (Two-hybrid), ZBTB8A (Two-hybrid), YES1 (Affinity Capture-MS), YES1 (Affinity Capture-MS), YES1 (Affinity Capture-MS)
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
18 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| YES1 | down-regulates | CDK4 | phosphorylation |
| YES1 | “up-regulates activity” | YES1 | phosphorylation |
| YES1 | “up-regulates activity” | WBP2 | phosphorylation |
| YES1 | “down-regulates activity” | YY1 | phosphorylation |
| YES1 | “up-regulates quantity by stabilization” | SOCS1 | phosphorylation |
| AXL | “up-regulates activity” | YES1 | phosphorylation |
| EPHA2 | “up-regulates activity” | YES1 | phosphorylation |
| YES1 | “up-regulates activity” | YAP1 | phosphorylation |
| YES1 | “up-regulates activity” | WWTR1 | phosphorylation |
| IL6ST | “up-regulates activity” | YES1 | phosphorylation |
| YES1 | “up-regulates activity” | ANXA2 | phosphorylation |
| YES1 | “up-regulates activity” | POU2F2 | phosphorylation |
| RPL10 | down-regulates | YES1 | binding |
| YES1 | “up-regulates activity” | GLO1 | phosphorylation |
| YES1 | “down-regulates activity” | SOCS1 | phosphorylation |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 128 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 |
|---|---|---|---|
| Signaling by PTK6 | 5 | 33.2× | 1e-04 |
| Signaling by Non-Receptor Tyrosine Kinases | 5 | 33.2× | 1e-04 |
| Downstream signal transduction | 5 | 23.2× | 5e-04 |
| Signaling by BRAF and RAF1 fusions | 5 | 10.4× | 5e-03 |
| Extra-nuclear estrogen signaling | 5 | 10.4× | 5e-03 |
| VEGFA-VEGFR2 Pathway | 6 | 10.2× | 3e-03 |
| PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 6 | 7.1× | 7e-03 |
| PIP3 activates AKT signaling | 8 | 6.5× | 3e-03 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| regulation of cell growth | 6 | 12.1× | 2e-03 |
| cell surface receptor protein tyrosine kinase signaling pathway | 7 | 11.1× | 2e-03 |
| T cell receptor signaling pathway | 7 | 9.7× | 2e-03 |
| regulation of apoptotic process | 11 | 8.3× | 8e-05 |
| negative regulation of gene expression | 9 | 5.7× | 4e-03 |
| cell migration | 10 | 5.6× | 2e-03 |
Disease & clinical
Cancer significance
Clinical variants and AI predictions
ClinVar
73 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 56 |
| Likely benign | 3 |
| Benign | 0 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
2531 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 18:724630:TAC:T | acceptor_gain | 1.0000 |
| 18:736802:TTTTA:T | donor_loss | 1.0000 |
| 18:736803:TTTA:T | donor_loss | 1.0000 |
| 18:736804:TTACC:T | donor_loss | 1.0000 |
| 18:736805:TACC:T | donor_loss | 1.0000 |
| 18:736806:A:T | donor_loss | 1.0000 |
| 18:736807:CCTTG:C | donor_loss | 1.0000 |
| 18:736958:CAAT:C | acceptor_gain | 1.0000 |
| 18:736960:AT:A | acceptor_gain | 1.0000 |
| 18:736962:C:CC | acceptor_gain | 1.0000 |
| 18:736963:T:C | acceptor_gain | 1.0000 |
| 18:736963:T:TC | acceptor_gain | 1.0000 |
| 18:739731:ATAC:A | donor_loss | 1.0000 |
| 18:739732:TAC:T | donor_loss | 1.0000 |
| 18:739733:A:AT | donor_loss | 1.0000 |
| 18:739734:CC:C | donor_loss | 1.0000 |
| 18:739813:T:C | acceptor_loss | 1.0000 |
| 18:739835:A:C | acceptor_gain | 1.0000 |
| 18:742915:TACCT:T | donor_loss | 1.0000 |
| 18:742916:A:AC | donor_gain | 1.0000 |
| 18:742916:AC:A | donor_gain | 1.0000 |
| 18:742916:ACC:A | donor_loss | 1.0000 |
| 18:742917:C:CC | donor_gain | 1.0000 |
| 18:742917:CC:C | donor_gain | 1.0000 |
| 18:742917:CCT:C | donor_gain | 1.0000 |
| 18:742917:CCTT:C | donor_gain | 1.0000 |
| 18:743093:TGTTC:T | acceptor_gain | 1.0000 |
| 18:743094:GTTC:G | acceptor_gain | 1.0000 |
| 18:743095:TTC:T | acceptor_gain | 1.0000 |
| 18:743095:TTCCT:T | acceptor_loss | 1.0000 |
AlphaMissense
3527 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 18:724447:A:G | Y537H | 1.000 |
| 18:724499:A:C | F519L | 1.000 |
| 18:724499:A:T | F519L | 1.000 |
| 18:724500:A:G | F519S | 1.000 |
| 18:724501:A:G | F519L | 1.000 |
| 18:724501:A:T | F519I | 1.000 |
| 18:724508:T:A | R516S | 1.000 |
| 18:724508:T:G | R516S | 1.000 |
| 18:724509:C:A | R516I | 1.000 |
| 18:724509:C:G | R516T | 1.000 |
| 18:724510:T:C | R516G | 1.000 |
| 18:724531:A:G | W509R | 1.000 |
| 18:724531:A:T | W509R | 1.000 |
| 18:724584:A:G | M491T | 1.000 |
| 18:724611:A:G | L482S | 1.000 |
| 18:732840:A:C | Y473D | 1.000 |
| 18:732840:A:G | Y473H | 1.000 |
| 18:732840:A:T | Y473N | 1.000 |
| 18:732842:G:C | P472R | 1.000 |
| 18:732842:G:T | P472Q | 1.000 |
| 18:732843:G:A | P472S | 1.000 |
| 18:732843:G:T | P472T | 1.000 |
| 18:732851:C:A | G469V | 1.000 |
| 18:732851:C:T | G469D | 1.000 |
| 18:732852:C:G | G469R | 1.000 |
| 18:732863:A:G | L465P | 1.000 |
| 18:732867:C:T | E464K | 1.000 |
| 18:732875:A:G | L461P | 1.000 |
| 18:732881:C:A | G459V | 1.000 |
| 18:732881:C:T | G459E | 1.000 |
dbSNP variants (sampled 300 via entrez): RS1000033153 (18:780994 G>C), RS1000041115 (18:722911 T>A,C), RS1000060924 (18:806223 C>A,T), RS1000070719 (18:806439 A>C,G), RS1000113407 (18:727768 A>G), RS1000115534 (18:741729 G>C), RS1000120993 (18:728315 C>T), RS1000146467 (18:766246 C>G), RS1000157730 (18:794598 C>G,T), RS1000202568 (18:806598 G>A), RS1000240477 (18:814145 T>A,G), RS1000305583 (18:754616 C>A), RS1000313116 (18:814306 C>A,G), RS1000338429 (18:733026 G>A), RS1000339486 (18:730691 C>T)
Disease associations
OMIM: gene MIM:164880 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
13 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST001918_3 | Pulmonary function in asthmatics | 4.000000e-06 |
| GCST002279_44 | PR interval in Tripanosoma cruzi seropositivity | 3.000000e-07 |
| GCST005024_83 | Pursuit maintenance gain | 6.000000e-06 |
| GCST005978_3 | Diastolic blood pressure | 7.000000e-10 |
| GCST005979_4 | Systolic blood pressure | 5.000000e-11 |
| GCST006010_17 | Mean arterial pressure | 3.000000e-12 |
| GCST006624_106 | Systolic blood pressure | 2.000000e-21 |
| GCST007267_39 | Systolic blood pressure | 6.000000e-16 |
| GCST007703_77 | Systolic blood pressure | 3.000000e-11 |
| GCST007704_29 | Diastolic blood pressure | 1.000000e-08 |
| GCST007706_39 | Mean arterial pressure | 4.000000e-11 |
| GCST007707_40 | Hypertension | 7.000000e-07 |
| GCST009888_1 | Thyroid autoantibody positivity (anti-thyroglobulin (TgAb) and/or anti-thyroid peroxidase (TPOAb) levels) | 2.000000e-08 |
EFO canonical traits (6, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0003892 | pulmonary function measurement |
| EFO:0004462 | PR interval |
| EFO:0008433 | pursuit maintenance gain measurement |
| EFO:0006336 | diastolic blood pressure |
| EFO:0006335 | systolic blood pressure |
| EFO:0006340 | mean arterial pressure |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (3): CHEMBL2073 (SINGLE PROTEIN), CHEMBL2363074 (PROTEIN FAMILY), CHEMBL4523728 (PROTEIN-PROTEIN INTERACTION)
Molecules with ChEMBL bioactivity
66 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 433,199 (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 |
| CHEMBL1421 | DASATINIB ANHYDROUS | 4 | 55,003 |
| CHEMBL180022 | NERATINIB | 4 | 9,404 |
| CHEMBL1834657 | INFIGRATINIB PHOSPHATE | 4 | 285 |
| CHEMBL1852688 | INFIGRATINIB | 4 | 2,209 |
| 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 |
| CHEMBL3301622 | GILTERITINIB | 4 | 2,395 |
| CHEMBL3545311 | BRIGATINIB | 4 | 5,634 |
| CHEMBL477772 | PAZOPANIB | 4 | 15,540 |
| CHEMBL502835 | NINTEDANIB | 4 | 8,545 |
| CHEMBL535 | SUNITINIB | 4 | 79,020 |
| CHEMBL5416410 | DASATINIB | 4 | 655 |
| CHEMBL553 | ERLOTINIB | 4 | 108,300 |
| CHEMBL576982 | QUIZARTINIB | 4 | 4,432 |
| CHEMBL601719 | CRIZOTINIB | 4 | |
| CHEMBL608533 | MIDOSTAURIN | 4 | |
| CHEMBL1908391 | MASITINIB | 3 | |
| CHEMBL217092 | SARACATINIB | 3 | |
| CHEMBL31965 | CANERTINIB | 3 | |
| CHEMBL3544983 | TESEVATINIB | 3 | |
| CHEMBL491473 | CEDIRANIB | 3 | |
| CHEMBL50 | QUERCETIN | 3 | |
| CHEMBL522892 | DOVITINIB | 3 | |
| CHEMBL572881 | MOTESANIB | 3 |
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 (9 total), top 9:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| eCF506 | Inhibition | 9.3 | pIC50 |
| rebastinib | Inhibition | 8.82 | pIC50 |
| saracatinib | Inhibition | 8.4 | pIC50 |
| ibrutinib | Inhibition | 8.39 | pIC50 |
| nemtabrutinib | Inhibition | 8.38 | pIC50 |
| nefextinib | Inhibition | 8.24 | pIC50 |
| SU6656 | Inhibition | 7.7 | pIC50 |
| xiliertinib | Inhibition | 6.48 | pIC50 |
| spebrutinib | Inhibition | 6.14 | pIC50 |
Binding affinities (BindingDB)
78 measured of 99 human assays (99 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| 1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea | KD | 0.37 nM | |
| 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-(diethylaminomethoxy)phenyl]-7-(2,6-dimethylphenyl)-5-methyl-1,2,4-benzotriazin-3-amine | IC50 | 2.6 nM | US-8481536: Benzotriazine inhibitors of kinases |
| 5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one | KD | 2.8 nM | |
| 3-[[2-[3-(morpholin-4-ylmethyl)phenyl]thieno[3,2-b]pyridin-7-yl]amino]phenol | IC50 | 5.1 nM | US-9062066: Anti-inflammatory compound having inhibitory activity against multiple tyrosine kinases and pharmaceutical composition containing same |
| 3-[[7-(2-chloro-5-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]-N-[2-(dimethylamino)ethyl]benzamide | IC50 | 5.3 nM | US-8481536: Benzotriazine inhibitors of kinases |
| N-[2-[[5-chloro-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[2-[4-(4-methylpiperazin-1-yl)anilino]-5-(4-phenoxyphenyl)pyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[5-(4-acetylphenyl)-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[5-(6-methoxy-3-pyridinyl)-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[2-[4-(4-methylpiperazin-1-yl)anilino]-5-thiophen-2-ylpyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[2-[4-(4-methylpiperazin-1-yl)anilino]-5-[(4-phenoxyphenyl)methoxy]pyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-(2-chloro-6-methylphenyl)-2-[3-methyl-4-(4-methylpiperazin-1-yl)anilino]-4-[2-(prop-2-enoylamino)anilino]pyrimidine-5-carboxamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-(2-chloro-6-methylphenyl)-2-[4-(4-methylpiperazin-1-yl)anilino]-4-[2-(propanoylamino)anilino]pyrimidine-5-carboxamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[5-(furan-3-yl)-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-(2-chloro-6-methylphenyl)-2-[4-(4-methylpiperazin-1-yl)anilino]-4-[2-(prop-2-enoylamino)anilino]pyrimidine-5-carboxamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[5-[(4-methylphenyl)methoxy]-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[5-cyclopropyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[5-ethyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[5-bromo-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[5-methyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[5-iodo-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[2-[4-(4-methylpiperazin-1-yl)anilino]thieno[3,2-d]pyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-(2,6-dichlorophenyl)-2-[4-(4-methylpiperazin-1-yl)anilino]-4-[2-(prop-2-enoylamino)anilino]pyrimidine-5-carboxamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-(2,6-dimethylphenyl)-2-[4-(4-methylpiperazin-1-yl)anilino]-4-[2-(prop-2-enoylamino)anilino]pyrimidine-5-carboxamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[5-chloro-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]-5-methylphenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[5-chloro-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]-6-methylphenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[5-chloro-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]-3-fluorophenyl]prop-2-enamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-(2-chloro-6-methylphenyl)-4-[5-fluoro-2-(prop-2-enoylamino)anilino]-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-(2-chloro-6-methylphenyl)-4-[2-fluoro-6-(prop-2-enoylamino)anilino]-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide | IC50 | 5.5 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| 4-chloro-3-[6-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol | IC50 | 5.7 nM | US-8481536: Benzotriazine inhibitors of kinases |
| 7-(2,6-dimethylphenyl)-5-methyl-N-[3-(2-pyrrolidin-1-ylethoxy)phenyl]-1,2,4-benzotriazin-3-amine | IC50 | 6.4 nM | US-8481536: Benzotriazine inhibitors of kinases |
| 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 |
| BIIB-057 | IC50 | 10.5 nM | |
| tert-butyl 4-amino-3-[2-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]carbamoyl]phenyl]ethynyl]pyrazolo[3,4-d]pyrimidine-1-carboxylate | IC50 | 11 nM | US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof |
| 4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol | IC50 | 15.9 nM | US-8481536: Benzotriazine inhibitors of kinases |
| N-[3-[2-[4-amino-1-(1-methylpiperidin-4-yl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-3-(trifluoromethyl)benzamide | IC50 | 18 nM | US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof |
| 7-(2,6-dimethylphenyl)-5-methyl-N-[4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-1,2,4-benzotriazin-3-amine | IC50 | 21 nM | US-8481536: Benzotriazine inhibitors of kinases |
| 3-[2-[4-amino-1-(1-prop-2-enoylpiperidin-4-yl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide | IC50 | 22 nM | US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof |
| BMS-354825 | KD | 27 nM | |
| 4-[[7-(2-chloro-5-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide | IC50 | 30.8 nM | US-8481536: Benzotriazine inhibitors of kinases |
| 7-(2,6-dichlorophenyl)-5-methyl-N-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-1,2,4-benzotriazin-3-amine | IC50 | 40 nM | US-8481536: Benzotriazine inhibitors of kinases |
| N-[4-(2-cyclopentylethoxy)phenyl]-7-(2,6-dimethylphenyl)-5-methyl-1,2,4-benzotriazin-3-amine | IC50 | 49 nM | US-8481536: Benzotriazine inhibitors of kinases |
| N-(2-chloro-6-methylphenyl)-2-[3-(4-methylpiperazin-1-yl)anilino]-4-[2-(prop-2-enoylamino)anilino]pyrimidine-5-carboxamide | IC50 | 55 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[2-[4-(4-methylpiperazin-1-yl)anilino]furo[3,2-d]pyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 55 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[6-amino-5-chloro-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide | IC50 | 55 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| N-[2-[[5-chloro-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]-4-methylphenyl]prop-2-enamide | IC50 | 55 nM | US-12365664: Small molecule inhibitors of SRC tyrosine kinase |
| 7-(2-chlorophenyl)-5-methyl-N-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-1,2,4-benzotriazin-3-amine | IC50 | 58 nM | US-8481536: Benzotriazine inhibitors of kinases |
ChEMBL bioactivities
314 potent at pChembl≥5 of 333 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 9.52 | IC50 | 0.3 | nM | CHEMBL400402 |
| 9.52 | Kd | 0.3 | nM | DASATINIB |
| 9.41 | IC50 | 0.39 | nM | CHEMBL5280844 |
| 9.40 | IC50 | 0.4 | nM | BOSUTINIB |
| 9.30 | IC50 | 0.5 | nM | DASATINIB |
| 9.30 | IC50 | 0.5 | nM | CHEMBL400402 |
| 9.30 | IC50 | 0.5 | nM | CHEMBL364623 |
| 9.15 | IC50 | 0.7 | nM | SARACATINIB |
| 9.15 | IC50 | 0.7 | nM | CHEMBL3651257 |
| 9.10 | IC50 | 0.8 | nM | CHEMBL3426225 |
| 9.10 | IC50 | 0.8 | nM | CHEMBL3647967 |
| 9.05 | IC50 | 0.89 | nM | PONATINIB |
| 9.00 | Kd | 1 | nM | CHEMBL400402 |
| 9.00 | IC50 | 1 | nM | CHEMBL436137 |
| 9.00 | IC50 | 1 | nM | AT-9283 |
| 9.00 | IC50 | 1 | nM | CHEMBL4798527 |
| 9.00 | Kd | 1 | nM | CHEMBL249097 |
| 8.92 | IC50 | 1.2 | nM | CHEMBL3651296 |
| 8.92 | IC50 | 1.2 | nM | CHEMBL436137 |
| 8.91 | IC50 | 1.24 | nM | CHEMBL3651228 |
| 8.89 | IC50 | 1.28 | nM | CHEMBL249821 |
| 8.89 | IC50 | 1.3 | nM | CHEMBL249821 |
| 8.89 | IC50 | 1.3 | nM | CHEMBL5268244 |
| 8.85 | IC50 | 1.4 | nM | DOVITINIB |
| 8.82 | IC50 | 1.5 | nM | REBASTINIB |
| 8.77 | IC50 | 1.7 | nM | STAUROSPORINE |
| 8.70 | IC50 | 2 | nM | CHEMBL364623 |
| 8.70 | IC50 | 2 | nM | CHEMBL3426233 |
| 8.68 | IC50 | 2.1 | nM | CHEMBL2336005 |
| 8.64 | IC50 | 2.3 | nM | CHEMBL5280361 |
| 8.64 | Kd | 2.3 | nM | CHEMBL386051 |
| 8.63 | IC50 | 2.35 | nM | STAUROSPORINE |
| 8.62 | IC50 | 2.39 | nM | STAUROSPORINE |
| 8.60 | IC50 | 2.5 | nM | REBASTINIB |
| 8.59 | IC50 | 2.6 | nM | CHEMBL3651297 |
| 8.59 | IC50 | 2.6 | nM | CHEMBL218102 |
| 8.59 | IC50 | 2.56 | nM | STAUROSPORINE |
| 8.52 | IC50 | 3 | nM | CHEMBL457614 |
| 8.52 | IC50 | 3 | nM | CHEMBL217090 |
| 8.51 | IC50 | 3.1 | nM | CHEMBL231218 |
| 8.43 | IC50 | 3.7 | nM | CHEMBL218549 |
| 8.43 | Kd | 3.715 | nM | DASATINIB ANHYDROUS |
| 8.40 | IC50 | 4 | nM | CHEMBL3923175 |
| 8.40 | IC50 | 4 | nM | SARACATINIB |
| 8.40 | Kd | 4 | nM | DASATINIB |
| 8.40 | Kd | 4 | nM | DASATINIB ANHYDROUS |
| 8.40 | Kd | 4 | nM | BOSUTINIB |
| 8.39 | IC50 | 4.1 | nM | CHEMBL250625 |
| 8.39 | IC50 | 4.1 | nM | IBRUTINIB |
| 8.36 | IC50 | 4.4 | nM | STAUROSPORINE |
PubChem BioAssay actives
249 with measured affinity, of 2303 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 | 435328: Binding constant for YES kinase domain | kd | 0.0003 | uM |
| 4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol | 325210: Inhibition of YES | ic50 | 0.0003 | uM |
| (2-chloro-4-phenoxyphenyl)-[4-[[(6S)-6-(hydroxymethyl)oxan-3-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]methanone | 1939138: Inhibition of YES (unknown origin) | ic50 | 0.0004 | uM |
| Bosutinib | 507428: Inhibition of YES1 | 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 | 1310132: Inhibition of human YES using poly[Glu,Tyr]4:1 as substrate in presence of [gamma-33P] ATP | ic50 | 0.0005 | uM |
| N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine | 761477: Inhibition of Yes1 (unknown origin) by [gamma-33P]-ATP radiolabeled enzyme activity assay | ic50 | 0.0007 | 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 | 1206221: Inhibition of human Yes | ic50 | 0.0008 | uM |
| Ponatinib | 1716395: Binding affinity to human YES using poly[Glu:Tyr] (4:1) as substrate by radiometric hotspot kinase assay | ic50 | 0.0009 | uM |
| 7-(2,6-dimethylphenyl)-5-methyl-N-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-1,2,4-benzotriazin-3-amine | 276183: Inhibition of Yes | ic50 | 0.0010 | uM |
| N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide | 1734743: Inhibition of human full length recombinant YES using poly(Glu,Tyr)4:1 as substrate incubated for 40 mins in presence of [gamma33P-ATP] by radiometric scintillation counting analysis | ic50 | 0.0010 | uM |
| 1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea | 412621: Inhibition of Yes | ic50 | 0.0010 | uM |
| 3-[[4-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzamide | 389065: Binding affinity to human YES | kd | 0.0010 | uM |
| 4-[[7-(2-chloro-5-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide | 325210: Inhibition of YES | ic50 | 0.0013 | uM |
| [(2S,3R,4R,5R)-5-[4-amino-3-(4-methylphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]-3-methyl-4-prop-2-ynoxyoxolan-2-yl]methyl 4-fluorosulfonylbenzoate | 1940020: Inhibition of YES (unknown origin) | ic50 | 0.0013 | uM |
| 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one | 761477: Inhibition of Yes1 (unknown origin) by [gamma-33P]-ATP radiolabeled enzyme activity assay | ic50 | 0.0014 | uM |
| 4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide | 761477: Inhibition of Yes1 (unknown origin) by [gamma-33P]-ATP radiolabeled enzyme activity assay | ic50 | 0.0015 | 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 | 2198460: Inhibition of human YES using poly[Glu:Tyr] (4:1) as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by radiometric Hot-SpotSM Kinase assay | ic50 | 0.0017 | uM |
| N-(2-chloro-6-methylphenyl)-2-[(2,6-dimethylpyrimidin-4-yl)amino]-1,3-thiazole-5-carboxamide | 271968: Inhibition of Yes | ic50 | 0.0020 | uM |
| [(2S,3R,4R,5R)-5-[4-amino-3-(4-methylphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]-3-methyl-4-prop-2-ynoxyoxolan-2-yl]methyl ethenesulfonate | 1940020: Inhibition of YES (unknown origin) | ic50 | 0.0023 | uM |
| 6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one | 625018: Binding constant for YES kinase domain | kd | 0.0023 | uM |
| N-(5-chloro-1,3-benzodioxol-4-yl)-5-(oxan-4-yloxy)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine | 272224: Inhibition of recombinant C-YES by ELISA | ic50 | 0.0030 | uM |
| 5-chloro-2-N-[(1S)-1-(5-fluoro-2-pyridinyl)ethyl]-4-N-(3-propan-2-yloxy-1H-pyrazol-5-yl)pyrimidine-2,4-diamine | 761477: Inhibition of Yes1 (unknown origin) by [gamma-33P]-ATP radiolabeled enzyme activity assay | ic50 | 0.0030 | uM |
| Dasatinib | 2149796: Binding affinity to human YES1 incubated for 45 mins by Kinobead based pull down assay | kd | 0.0037 | uM |
| 2-[[N-[2-[3-ethylsulfonyl-4-(4-methylpiperazin-1-yl)anilino]-5-fluoropyrimidin-4-yl]-5-(hydroxymethyl)-2-methylanilino]methyl]benzonitrile | 1326072: Inhibition of N-terminal 6His-tagged full length recombinant human YES expressed in baculovirus expression system | ic50 | 0.0040 | uM |
| 4-chloro-3-[5-methyl-3-(4-piperidin-4-ylsulfonylanilino)-1,2,4-benzotriazin-7-yl]phenol | 325210: Inhibition of YES | ic50 | 0.0041 | uM |
| Ibrutinib | 2188603: Inhibition of recombinant YES1 (unknown origin) preincubated for 1 hr in presence of ATP by Z-Lyte assay | ic50 | 0.0041 | uM |
| 4-chloro-3-[5-methyl-3-[4-(3-pyrrolidin-1-ylpropyl)anilino]-1,2,4-benzotriazin-7-yl]phenol | 325210: Inhibition of YES | ic50 | 0.0048 | uM |
| 6-amino-7-(4-phenoxyphenyl)-9-[(3S)-1-prop-2-enoylpiperidin-3-yl]purin-8-one | 1425212: 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 | 0.0050 | uM |
| [4-[[7-(2-chloro-5-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]phenyl]-piperazin-1-ylmethanone | 325210: Inhibition of YES | ic50 | 0.0052 | uM |
| 7-(2,6-dichlorophenyl)-5-methyl-N-[4-[2-(1-oxidopyrrolidin-1-ium-1-yl)ethoxy]phenyl]-1,2,4-benzotriazin-3-amine | 330573: Inhibition of Yes by luminescence based kinase assay | ki | 0.0060 | uM |
| 4-methyl-3-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]-N-[3-(trifluoromethyl)phenyl]benzamide | 761478: Inhibition of Yes1 (unknown origin) assessed as kinase-dependent enzymatic production of ADP from ATP using coupled luminescence-based reaction by ADP-Glo kinase assay | ic50 | 0.0087 | uM |
| (3Z)-3-[[3-[3-(dimethylamino)propyl]-4,5,6,7-tetrahydro-1H-indol-2-yl]methylidene]-N-methyl-2-oxo-1H-indole-5-sulfonamide | 220258: Inhibitory activity against Yes tyrosine kinase | ic50 | 0.0100 | uM |
| 3-[2-[(Z)-[5-(methylsulfamoyl)-2-oxo-1H-indol-3-ylidene]methyl]-4,5,6,7-tetrahydro-1H-indol-3-yl]propanamide | 220258: Inhibitory activity against Yes tyrosine kinase | ic50 | 0.0100 | uM |
| 2-[4-[3-[2-[(Z)-[5-(methylsulfamoyl)-2-oxo-1H-indol-3-ylidene]methyl]-4,5,6,7-tetrahydro-1H-indol-3-yl]propyl]piperazin-1-yl]acetic acid | 220258: Inhibitory activity against Yes tyrosine kinase | ic50 | 0.0100 | uM |
| 7-(2,6-dichlorophenyl)-5-methyl-N-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-1,2,4-benzotriazin-3-amine | 325210: Inhibition of YES | ic50 | 0.0100 | uM |
| 2-[4-[3-[2-[(Z)-(5-ethylsulfonyl-2-oxo-1H-indol-3-ylidene)methyl]-4,5,6,7-tetrahydro-1H-indol-3-yl]propyl]piperazin-1-yl]acetic acid | 220258: Inhibitory activity against Yes tyrosine kinase | ic50 | 0.0100 | uM |
| (3Z)-3-[[3-[3-(4-hydroxypiperidin-1-yl)propyl]-4,5,6,7-tetrahydro-1H-indol-2-yl]methylidene]-N-methyl-2-oxo-1H-indole-5-sulfonamide | 220258: Inhibitory activity against Yes tyrosine kinase | ic50 | 0.0100 | uM |
| (3Z)-N-methyl-3-[[3-[3-(4-methylpiperazin-1-yl)propyl]-4,5,6,7-tetrahydro-1H-indol-2-yl]methylidene]-2-oxo-1H-indole-5-sulfonamide | 220258: Inhibitory activity against Yes tyrosine kinase | ic50 | 0.0100 | uM |
| (3Z)-3-[[3-[3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl]-4,5,6,7-tetrahydro-1H-indol-2-yl]methylidene]-N-methyl-2-oxo-1H-indole-5-sulfonamide | 220258: Inhibitory activity against Yes tyrosine kinase | ic50 | 0.0100 | uM |
| 1-[2-[4-[(dimethylamino)methyl]piperidin-1-yl]ethyl]-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[3,4-d]pyrimidin-4-amine | 1310132: Inhibition of human YES using poly[Glu,Tyr]4:1 as substrate in presence of [gamma-33P] ATP | ic50 | 0.0120 | 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 | 1721761: Inhibition of YES1 (unknown origin) | ic50 | 0.0120 | uM |
| 6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine | 761477: Inhibition of Yes1 (unknown origin) by [gamma-33P]-ATP radiolabeled enzyme activity assay | ic50 | 0.0131 | uM |
| [4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone | 625018: Binding constant for YES kinase domain | kd | 0.0180 | uM |
| Brigatinib | 2182804: Inhibition of human YES1 using poly (Glu, Tyr)4:1 as substrate in presence of [gamma33P]-ATP by HotSpot assay | ic50 | 0.0190 | uM |
| 3-chloro-4-[3-(5-chloro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide | 1678397: Inhibition of YES1 (unknown origin) | ic50 | 0.0190 | uM |
| ethyl 2-[4-[3-[2-[(Z)-[5-(methylsulfamoyl)-2-oxo-1H-indol-3-ylidene]methyl]-4,5,6,7-tetrahydro-1H-indol-3-yl]propyl]piperazin-1-yl]acetate | 220258: Inhibitory activity against Yes tyrosine kinase | ic50 | 0.0200 | uM |
| (3Z)-5-ethylsulfonyl-3-[[3-[3-(4-hydroxypiperidin-1-yl)propyl]-4,5,6,7-tetrahydro-1H-indol-2-yl]methylidene]-1H-indol-2-one | 220258: Inhibitory activity against Yes tyrosine kinase | ic50 | 0.0200 | uM |
| (3Z)-N,N-dimethyl-2-oxo-3-(4,5,6,7-tetrahydro-1H-indol-2-ylmethylidene)-1H-indole-5-sulfonamide | 325713: Inhibition of Yes kinase | ic50 | 0.0200 | uM |
| (3Z)-3-[[3-[3-(dimethylamino)propyl]-4,5,6,7-tetrahydro-1H-indol-2-yl]methylidene]-5-ethylsulfonyl-1H-indol-2-one | 220258: Inhibitory activity against Yes tyrosine kinase | ic50 | 0.0200 | 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 | 1711668: Inhibition of human YES1 | ic50 | 0.0210 | uM |
CTD chemical–gene interactions
64 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| bisphenol A | decreases expression, increases expression | 2 |
| sodium arsenite | increases abundance, increases expression | 2 |
| Arsenic | affects methylation, increases abundance, increases expression | 2 |
| Benzo(a)pyrene | decreases expression, affects methylation | 2 |
| Tobacco Smoke Pollution | affects expression, increases expression | 2 |
| aristolochic acid I | decreases expression | 1 |
| 3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide | decreases expression | 1 |
| bisphenol F | increases expression | 1 |
| 2,4,6-tribromophenol | increases expression | 1 |
| triphenyl phosphate | affects expression | 1 |
| alpha-pinene | affects cotreatment, increases oxidation, increases abundance | 1 |
| pyrogallol 1,3-dimethyl ether | increases expression, affects cotreatment, affects localization | 1 |
| decabromobiphenyl ether | increases expression | 1 |
| 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid | affects methylation, increases abundance | 1 |
| cobaltous chloride | increases phosphorylation, increases expression, increases secretion, decreases reaction | 1 |
| 2-bromopalmitate | decreases reaction, increases abundance, increases palmitoylation | 1 |
| benzo(e)pyrene | decreases methylation | 1 |
| 4-hydroxy-2-nonenal | decreases expression | 1 |
| 1-hydroxypyrene | affects cotreatment, decreases methylation | 1 |
| HC toxin | increases expression | 1 |
| methacrylaldehyde | affects cotreatment, increases oxidation, increases abundance | 1 |
| dibenzo(a,l)pyrene | decreases expression | 1 |
| chromium hexavalent ion | decreases activity | 1 |
| perfluorooctane sulfonic acid | decreases expression | 1 |
| CGP 52608 | affects binding, increases reaction | 1 |
| K 7174 | increases expression | 1 |
| 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide | increases expression | 1 |
| bisphenol B | increases expression | 1 |
| 6-O-carboxypropyl-alpha-tocotrienol | decreases reaction, increases phosphorylation | 1 |
| bisphenol S | increases expression | 1 |
ChEMBL screening assays
514 unique, capped per target: 509 binding, 3 admet, 2 functional
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1009922 | Binding | Inhibition of Yes | Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. — J Med Chem |
| CHEMBL2354304 | Functional | PubChem BioAssay. qHTS for small molecule inhibitors of Yes1 kinase: Confirmatory screen on the cherrypicks. (Class of assay: confirmatory) | PubChem BioAssay data set |
| CHEMBL4313108 | ADMET | Inhibition of recombinant full-length human Yes at 100 nM using poly(Glu, Tyr) 4:1 as substrate measured after 40 mins in presence of [gamma33P]ATP by scintillation counting method | Discovery and Development of a Series of Pyrazolo[3,4-d]pyridazinone Compounds as the Novel Covalent Fibroblast Growth Factor Receptor Inhibitors by the Rational Drug Design. — J Med Chem |
Cellosaurus cell lines
6 cell lines: 6 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_B2LK | Abcam HeLa YES1 KO | Cancer cell line | Female |
| CVCL_C8IN | K562/fes clone WS-1 | Cancer cell line | Female |
| CVCL_C8IP | K562/fes clone WS-5 | Cancer cell line | Female |
| CVCL_C8IQ | K562/fes clone WS-6 | Cancer cell line | Female |
| CVCL_TY45 | HAP1 YES1 (-) 1 | Cancer cell line | Male |
| CVCL_TY46 | HAP1 YES1 (-) 2 | Cancer cell line | Male |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
- Targeted by drugs: Ibrutinib, Nemtabrutinib, Saracatinib
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): hypertensive disorder