MET

Summary

MET (MET proto-oncogene, receptor tyrosine kinase, HGNC:7029) is a protein-coding gene on chromosome 7q31.2, encoding Hepatocyte growth factor receptor (P08581). Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand.

This gene encodes a member of the receptor tyrosine kinase family of proteins and the product of the proto-oncogene MET. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that are linked via disulfide bonds to form the mature receptor. Further processing of the beta subunit results in the formation of the M10 peptide, which has been shown to reduce lung fibrosis. Binding of its ligand, hepatocyte growth factor, induces dimerization and activation of the receptor, which plays a role in cellular survival, embryogenesis, and cellular migration and invasion. Mutations in this gene are associated with papillary renal cell carcinoma, hepatocellular carcinoma, and various head and neck cancers. Amplification and overexpression of this gene are also associated with multiple human cancers.

Source: NCBI Gene 4233 — RefSeq curated summary.

At a glance

• Gene–disease (curated): papillary renal cell carcinoma (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 23
• Clinical variants (ClinVar): 4,867 total — 6 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 2
• Druggable target: yes — 95 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000245

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7029
Approved symbol	MET
Name	MET proto-oncogene, receptor tyrosine kinase
Location	7q31.2
Locus type	gene with protein product
Status	Approved
Aliases	HGFR, RCCP2, DFNB97
Ensembl gene	ENSG00000105976
Ensembl biotype	protein_coding
OMIM	164860
Entrez	4233

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000318493, ENST00000397752, ENST00000422097, ENST00000436117, ENST00000454623, ENST00000456159, ENST00000495962, ENST00000917365, ENST00000950406, ENST00000950407

RefSeq mRNA: 4 — MANE Select: NM_000245 NM_000245, NM_001127500, NM_001324401, NM_001324402

CCDS: CCDS43636, CCDS47689

Canonical transcript exons

ENST00000397752 — 21 exons

Exon	Start	End
ENSE00000717791	116763050	116763268
ENSE00000717803	116769645	116769791
ENSE00000717811	116771498	116771654
ENSE00000717833	116771849	116771989
ENSE00000717861	116774881	116775111
ENSE00000717902	116781988	116782097
ENSE00000717928	116783304	116783469
ENSE00000717937	116795655	116795791
ENSE00001530016	116759391	116759490
ENSE00001619404	116758459	116758620
ENSE00001898661	116795887	116798377
ENSE00003596200	116777389	116777469
ENSE00003663921	116778776	116778957
ENSE00004014102	116739950	116740084
ENSE00004014105	116757638	116757774
ENSE00004014106	116740852	116741025
ENSE00004014112	116731668	116731859
ENSE00004014113	116757437	116757539
ENSE00004014114	116672196	116672577
ENSE00004014116	116755355	116755515
ENSE00004014119	116699071	116700284

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 98.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.5126 / max 1025.8614, expressed in 1328 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80664	14.2331	1235
80660	2.0273	530
80665	0.8300	343
80663	0.6089	306
80661	0.2867	133
80677	0.2280	125
80662	0.2151	95
80667	0.1945	93
80671	0.1943	84
80668	0.1725	79

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	98.73	gold quality
germinal epithelium of ovary	UBERON:0001304	98.72	gold quality
cartilage tissue	UBERON:0002418	97.18	gold quality
parietal pleura	UBERON:0002400	96.61	gold quality
calcaneal tendon	UBERON:0003701	96.28	gold quality
middle temporal gyrus	UBERON:0002771	96.11	gold quality
bronchial epithelial cell	CL:0002328	95.94	gold quality
pleura	UBERON:0000977	95.79	gold quality
visceral pleura	UBERON:0002401	94.85	gold quality
epithelium of bronchus	UBERON:0002031	94.76	gold quality
nephron tubule	UBERON:0001231	94.73	gold quality
bronchus	UBERON:0002185	94.36	gold quality
nasal cavity epithelium	UBERON:0005384	93.93	gold quality
pancreatic ductal cell	CL:0002079	93.69	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.55	gold quality
gluteal muscle	UBERON:0002000	93.39	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.34	gold quality
colonic mucosa	UBERON:0000317	92.53	gold quality
biceps brachii	UBERON:0001507	92.28	gold quality
placenta	UBERON:0001987	92.28	gold quality
lower lobe of lung	UBERON:0008949	92.20	gold quality
epithelial cell of pancreas	CL:0000083	92.16	gold quality
skin of hip	UBERON:0001554	92.14	gold quality
palpebral conjunctiva	UBERON:0001812	92.10	gold quality
mucosa of urinary bladder	UBERON:0001259	92.08	gold quality
tendon	UBERON:0000043	92.00	gold quality
kidney epithelium	UBERON:0004819	91.39	gold quality
seminal vesicle	UBERON:0000998	91.38	gold quality
amniotic fluid	UBERON:0000173	91.31	gold quality
gingival epithelium	UBERON:0001949	91.12	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	1055.09
E-GEOD-135922	yes	8.39
E-ENAD-27	yes	6.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CREB3, CTNNB1, EGR1, ETS1, FOXP2, HIF1A, HTATIP2, JUN, MACC1, MITF, MYC, NFKB, NKX2-1, NME1, PAX3, PAX5, PAX6, RBPJ, RELA, SMAD2, SMAD3, SMAD4, SMAD7, SOX10, SP1, SP3, SPI1, STAT1, STAT3, TFCP2, TFE3, TP53, YBX1

miRNA regulators (miRDB)

160 targeting MET, 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-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-34C-5P	99.97	70.45	1577

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition (PMID:11750879)
• Modulation of the c-Met/hepatocyte growth factor pathway in small cell lung cancer (PMID:11839685)
• Met sequesters Fas, preventing apoptosis. (PMID:11864613)
• The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met (PMID:11894096)
• Increased c-Met expression participates in cholangiocarcinogenesis and in the early developmental stages of intrahepatic cholangiocarcinoma. (PMID:11895493)
• high expression seen in intermediate cells in normal and malignant prostate epithelium indicates they are prone to stromal invasion in prostate carcinoma (PMID:11948964)
• HGF and HGFR have an alternative role activating the via STAT3 transdution and operating on placental tissues, overall in organogenesis alteration conditions (PMID:12168776)
• a signal transduction cascade or cross-talk emanating from CD44 to c-Met (PMID:12183053)
• Overexpression of HGF/c-met appears to be a biological feedback response to the fibrotic process of systemic sclerosis. (PMID:12233882)
• MET signaling is negatively regulated by c-Cbl which induces ubiquitination of its cytoplasmic domain. (PMID:12244174)
• MET may be one of the long sought oncogenes controlling progression of primary cancers to metastasis. (PMID:12460923)
• immunoexpression of hepatocyte growth factor and c-Met in the eutopic endometrium of patients with pelvic endometrioisis is possibly useful to predict greater activity of the ectopic endometrium (PMID:12524084)
• HGF may have a role in the pathogenesis of papillary thyroid carcinoma (PMID:12538453)
• Radiation stimulates HGF receptor/c-Met expression that leads to amplifying cellular response to HGF stimulation via upregulated receptor tyrosine phosphorylation and MAP kinase activity in pancreatic cancer cells. (PMID:12594808)
• up-regulated during the in vitro recapitulation of several steps of angiogenesis; expression increased shortly after switching to angiogenic growth conditions & remained high during the first steps of angiogenesis, including cell migration & proliferation (PMID:12595309)
• Activation of the c-Met pathway targets the PI3K pathway in small cell lung cancer (PMID:12611639)
• These results indicate that overexpression of hepatocyte growth factor receptor tyrosine kinase in renal carcinoma cells participates in rapid tumor growth in vivo. (PMID:12646256)
• Ki-ras mutations and HGF signaling cooperate to enhance tumor growth by increased duration of MAPK activation and decreased apoptosis in human carcinoma cells. (PMID:12651912)
• Met is expressed by the majority of MM cell lines and by approximately half of the primary plasma cell neoplasms tested.The hepatocyte growth factor/Met pathway controls proliferation and apoptosis in multiple myeloma. (PMID:12682635)
• Endosomal dynamics of Met determine signaling output. (PMID:12686592)
• Autocrine and paracrine support of HGF-c-Met system attenuates degeneration of anterior horn cells in amyotrophic lateral sclerosis. Disruption of neuronal HGF-c-Met system at advanced stage accelerates cellular degeneration and cell death. (PMID:12707786)
• Role of the HGF receptor in proliferation and invasive behavior of osteosarcoma cell lines. (PMID:12709413)
• data define a protein kinase c-controlled traffic pathway for c-Met that operates independently of its degradative pathway (PMID:12716900)
• hypoxia promotes tumor invasion by sensitizing cells to hepatocyte growth factor stimulation, providing a molecular basis to explain Met overexpression in cancer (PMID:12726861)
• Gab1 and the Met receptor interact in a novel manner, such that the activated kinase domain of Met and the negative charge of phosphotyrosine 1349 engage the Gab1 MBD as an extended peptide ligand (PMID:12766170)
• Met can be detected in the axillary fluids of patients who undergo conservative operations for breast cancer, and its expression in the axillary drainage may have potential as a prognostic factor. (PMID:12793903)
• N-terminal domain of HGF inhibits angiogenesis not by disrupting the HGF/c-met interaction but rather by interfering with the endothelial glycosaminoglycans. (PMID:12847110)
• Activation of c-Met in colorectal carcinoma cells leads to constitutive association of tyrosine-phosphorylated beta-catenin (PMID:12856716)
• hepatocyte growth factor and c-Met/HGF receptor have roles in prostate neoplasm progression (PMID:12883672)
• c-Met signaling has roles in scattering, angiogenesis, proliferation, enhanced cell motility, invasion, and eventual metastasis [review] (PMID:12884908)
• These data suggest that coexpression of the MET and RON receptors confer a selective advantage to ovarian cancer cells and might promote ovarian cancer progression. (PMID:12915129)
• C-met expression is a significant marker for tall cell variant papillary carcinoma of the thyroid gland. (PMID:14508824)
• MUC1 and Met can be detected in the axillary fluids of patients with breast cancer; the expression of both tumor markers in the axillary drainage is strongly associated with unfavorable tumor features and can be used as a prognostic factor (PMID:14509156)
• Retroviral ribozyme transgenes targeting HGF/SF in fibroblasts or its receptor cMET in mammary cancer cells can reduce the growth of mammary cancer and associated angiogenesis by inhibiting paracrine stromal-tumor cell interactions. (PMID:14519655)
• c-Met and HGF-SF have roles in the growth and progression of human and canine osteosarcoma (PMID:14524531)
• establish by deletion mutagenesis that the HGF/SF and heparin-binding sites of MET are contained within a large N-terminal domain spanning the alpha-chain (amino acids 25-307) and the first 212 amino acids of the beta-chain (amino acids 308-519) (PMID:14528000)
• Mutation present in a notable subset of patients with oropharyngeal cancer and may interfere with radioresponsiveness. (PMID:14627992)
• Differentially expressed in gastric cancer and intestinal metaplasia. (PMID:14719064)
• Ser-985 phosphorylation of c-Met is bi-directionally regulated through PKC and PP2A (PMID:15075332)
• Data identify a DpYR motif including tyrosine(1003) as being important for the direct recruitment of the c-Cbl tyrosine kinase binding domain and for ubiquitination of the Met receptor. (PMID:15123609)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	met	ENSDARG00000070903
mus_musculus	Met	ENSMUSG00000009376
rattus_norvegicus	Met	ENSRNOG00000052745

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715)

Protein

Protein identifiers

Hepatocyte growth factor receptor — P08581 (reviewed: P08581)

Alternative names: HGF/SF receptor, Proto-oncogene c-Met, Scatter factor receptor, Tyrosine-protein kinase Met

All UniProt accessions (4): P08581, C9JKM5, E6Y365, H7C130

UniProt curated annotations — full annotation on UniProt →

Function. Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of neuronal precursors, angiogenesis and kidney formation. During skeletal muscle development, it is crucial for the migration of muscle progenitor cells and for the proliferation of secondary myoblasts. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Also promotes differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis. (Microbial infection) Acts as a receptor for Listeria monocytogenes internalin InlB, mediating entry of the pathogen into cells.

Subunit / interactions. Heterodimer made of an alpha chain (50 kDa) and a beta chain (145 kDa) which are disulfide linked. Binds PLXNB1. Interacts when phosphorylated with downstream effectors including STAT3, PIK3R1, SRC, PCLG1, GRB2 and GAB1. Interacts with SPSB1, SPSB2 and SPSB4. Interacts with INPP5D/SHIP1. When phosphorylated at Tyr-1356, interacts with INPPL1/SHIP2. Interacts with RANBP9 and RANBP10, as well as SPSB1, SPSB2, SPSB3 and SPSB4. SPSB1 binding occurs in the presence and in the absence of HGF, however HGF treatment has a positive effect on this interaction. Interacts with MUC20; prevents interaction with GRB2 and suppresses hepatocyte growth factor-induced cell proliferation. Interacts with GRB10. Interacts with PTPN1 and PTPN2. Interacts with LECT2; this interaction may have an antagonistic effect on receptor activation. Interacts with HSP90AA1 and HSP90AB1; the interaction suppresses MET kinase activity. Interacts with tensin TNS3. Interacts (when phosphorylated) with tensin TNS4 (via SH2 domain); the interaction increases MET protein stability by inhibiting MET endocytosis and subsequent lysosomal degradation. (Microbial infection) Interacts via extracytoplasmic residues 25-656 with L.monocytogenes InlB; MET can bind HGF, its endogenous ligand, and InlB simultaneously. InlB probably dimerizes upon binding to MET, which encourages subsequent dimerization of MET.

Subcellular location. Membrane Secreted.

Tissue specificity. Expressed in normal hepatocytes as well as in epithelial cells lining the stomach, the small and the large intestine. Found also in basal keratinocytes of esophagus and skin. High levels are found in liver, gastrointestinal tract, thyroid and kidney. Also present in the brain. Expressed in metaphyseal bone (at protein level).

Post-translational modifications. Autophosphorylated in response to ligand binding on Tyr-1234 and Tyr-1235 in the kinase domain leading to further phosphorylation of Tyr-1349 and Tyr-1356 in the C-terminal multifunctional docking site. Dephosphorylated by PTPRJ at Tyr-1349 and Tyr-1365. Dephosphorylated by PTPN1 and PTPN2. Ubiquitinated. Ubiquitination by CBL regulates MET endocytosis, resulting in decreasing plasma membrane receptor abundance, and in endosomal degradation and/or recycling of internalized receptors. O-mannosylation of IPT/TIG domains by TMEM260 is required for protein maturation. O-mannosylated residues are composed of single mannose glycans that are not elongated or modified. (Microbial infection) Tyrosine phosphorylation is stimulated by L.monocytogenes InlB. Tyrosine phosphorylation is maximal 10-20 minutes after treatment with InlB and disappears by 60 minutes. The phosphorylated residues were not identified.

Disease relevance. Activation of MET after rearrangement with the TPR gene produces an oncogenic protein. Defects in MET may be associated with gastric cancer. Hepatocellular carcinoma (HCC) [MIM:114550] A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. The disease is caused by variants affecting the gene represented in this entry. Renal cell carcinoma papillary (RCCP) [MIM:605074] A subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. The disease is caused by variants affecting the gene represented in this entry. A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes. MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies. Deafness, autosomal recessive, 97 (DFNB97) [MIM:616705] A form of non-syndromic sensorineural hearing loss with prelingual onset. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry. Osteofibrous dysplasia (OSFD) [MIM:607278] A congenital disorder of osteogenesis characterized by non-neoplastic, radiolucent lesions that affect the cortical bone immediately under the periosteum. It usually manifests as a painless swelling or anterior bowing of the long bones, most commonly the tibia and fibula. Disease susceptibility is associated with variants affecting the gene represented in this entry. Disease-associated variants identified in 4 families cause the deletion of exon 14. This results in the exclusion of an ubiquitination target site within the cytoplasmic domain, hence in protein stabilization. The persistent presence of MET at the cell surface in conditions of ligand-dependent activation retards osteoblastic differentiation. Arthrogryposis, distal, 11 (DA11) [MIM:620019] A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA11 is an autosomal dominant form characterized mainly by camptodactyly. Other features include absent flexion creases and limited forearm supination. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. In its inactive state, the C-terminal tail interacts with the catalytic domain and inhibits the kinase activity. Upon ligand binding, the C-terminal tail is displaced and becomes phosphorylated, thus increasing the kinase activity.

Domain organisation. The kinase domain is involved in SPSB1 binding. The beta-propeller Sema domain mediates binding to HGF.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P08581-1	1	yes
P08581-2	2
P08581-3	3, Soluble MET variant 4

RefSeq proteins (4): NP_000236, NP_001120972, NP_001311330, NP_001311331 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001627	Semap_dom	Domain
IPR002165	Plexin_repeat	Repeat
IPR002909	IPT_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016201	PSI	Domain
IPR016244	Tyr_kinase_HGF/MSP_rcpt	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR031148	Plexin	Family
IPR036352	Semap_dom_sf	Homologous_superfamily

Pfam: PF01403, PF01437, PF01833, PF07714

Enzyme classification (BRENDA):

• EC 2.7.10.1 — receptor protein-tyrosine kinase (BRENDA: 44 organisms, 214 substrates, 574 inhibitors, 11 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0011–0.129	4
AC-DYFE-6-CHLORO-W-NHME	0.0051	1
AC-DYFGW-NHME	0.07	1
YFEW	0.232	1

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (224 total): strand 74, sequence variant 37, helix 33, glycosylation site 14, modified residue 13, disulfide bond 12, turn 9, mutagenesis site 6, sequence conflict 5, domain 5, site 3, splice variant 3, region of interest 2, binding site 2, topological domain 2, signal peptide 1, chain 1, active site 1, transmembrane region 1

Structure

Experimental structures (PDB)

130 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9T6K	X-RAY DIFFRACTION	1.13
9T0D	X-RAY DIFFRACTION	1.2
4R1V	X-RAY DIFFRACTION	1.2
9SXJ	X-RAY DIFFRACTION	1.31
3BUX	X-RAY DIFFRACTION	1.35
3F66	X-RAY DIFFRACTION	1.4
3ZCL	X-RAY DIFFRACTION	1.4
9T08	X-RAY DIFFRACTION	1.46
3DKC	X-RAY DIFFRACTION	1.52
9T0B	X-RAY DIFFRACTION	1.54
9C1R	X-RAY DIFFRACTION	1.59
3Q6U	X-RAY DIFFRACTION	1.6
9T3Q	X-RAY DIFFRACTION	1.63
4MXC	X-RAY DIFFRACTION	1.63
5HTI	X-RAY DIFFRACTION	1.66
9T2V	X-RAY DIFFRACTION	1.67
6SDC	X-RAY DIFFRACTION	1.67
7V3R	X-RAY DIFFRACTION	1.7
5HNI	X-RAY DIFFRACTION	1.71
3Q6W	X-RAY DIFFRACTION	1.75
4XMO	X-RAY DIFFRACTION	1.75
5EOB	X-RAY DIFFRACTION	1.75
7B3Q	X-RAY DIFFRACTION	1.75
7B40	X-RAY DIFFRACTION	1.76
7B44	X-RAY DIFFRACTION	1.76
8OUU	X-RAY DIFFRACTION	1.77
8OUV	X-RAY DIFFRACTION	1.78
1R0P	X-RAY DIFFRACTION	1.8
1R1W	X-RAY DIFFRACTION	1.8
3DKF	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08581-F1	79.28	0.43

Antibody-complex structures (SAbDab): 4 — 4K3J, 5LSP, 6I04, 6WVZ

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 (4): 1204 (proton acceptor); 307–308 (cleavage); 1003 (required for ligand-induced cbl-mediated ubiquitination); 1009–1010 (breakpoint for translocation to form tpr-met oncogene)

Ligand- & substrate-binding residues (2): 1084–1092; 1110

Post-translational modifications (13): 966, 977, 990, 997, 1000, 1003, 1230, 1234, 1235, 1289, 1349, 1356, 1365

Disulfide bonds (12): 95–101, 98–160, 133–141, 172–175, 298–363, 385–397, 520–538, 526–561, 529–545, 541–551, 610–624, 697–709

Glycosylation sites (14): 45, 106, 149, 202, 399, 405, 582, 607, 635, 676, 761, 785, 879, 930

Mutagenesis-validated functional residues (6):

Position	Phenotype
1349	no effect on ligand-induced cbl-mediated ubiquitination; when associated with f-1313, f-1356 and f-1365.
1356	no effect on ligand-induced cbl-mediated ubiquitination; when associated with f-1313, f-1349 and f-1365.
1365	no effect on ligand-induced cbl-mediated ubiquitination; when associated with f-1313, f-1349 and f-1356.
1234	complete loss of kinase activity and of ligand-induced ubiquitination. alters interaction with ptpn1 and ptpn2. loss of
1235	complete loss of kinase activity. alters interaction with ptpn1 and ptpn2. loss of interaction with ptpn1 and ptpn2; whe
1313	no effect on ligand-induced cbl-mediated ubiquitination; when associated with f-1349, f-1356 and f-1365.

Function

Pathways and Gene Ontology

Reactome pathways

44 pathways

ID	Pathway
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-416550	Sema4D mediated inhibition of cell attachment and migration
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6806942	MET Receptor Activation
R-HSA-6807004	Negative regulation of MET activity
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8851805	MET activates RAS signaling
R-HSA-8851907	MET activates PI3K/AKT signaling
R-HSA-8865999	MET activates PTPN11
R-HSA-8874081	MET activates PTK2 signaling
R-HSA-8875360	InlB-mediated entry of Listeria monocytogenes into host cell
R-HSA-8875513	MET interacts with TNS proteins
R-HSA-8875555	MET activates RAP1 and RAC1
R-HSA-8875656	MET receptor recycling
R-HSA-8875791	MET activates STAT3
R-HSA-9022699	MECP2 regulates neuronal receptors and channels
R-HSA-9734091	Drug-mediated inhibition of MET activation
R-HSA-9825892	Regulation of MITF-M-dependent genes involved in cell cycle and proliferation
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-199418	Negative regulation of the PI3K/AKT network
R-HSA-212436	Generic Transcription Pathway
R-HSA-2219528	PI3K/AKT Signaling in Cancer
R-HSA-373755	Semaphorin interactions
R-HSA-400685	Sema4D in semaphorin signaling
R-HSA-422475	Axon guidance
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-5663205	Infectious disease

MSigDB gene sets: 0 (showing top):

GO Biological Process (26): endothelial cell morphogenesis (GO:0001886), liver development (GO:0001889), cell surface receptor signaling pathway (GO:0007166), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), negative regulation of autophagy (GO:0010507), neuron differentiation (GO:0030182), pancreas development (GO:0031016), positive regulation of transcription by RNA polymerase II (GO:0045944), hepatocyte growth factor receptor signaling pathway (GO:0048012), branching morphogenesis of an epithelial tube (GO:0048754), positive chemotaxis (GO:0050918), excitatory postsynaptic potential (GO:0060079), semaphorin-plexin signaling pathway (GO:0071526), negative regulation of hydrogen peroxide-mediated programmed cell death (GO:1901299), positive regulation of endothelial cell chemotaxis (GO:2001028), protein phosphorylation (GO:0006468), signal transduction (GO:0007165), regulation of gene expression (GO:0010468), positive regulation of microtubule polymerization (GO:0031116), negative regulation of Rho protein signal transduction (GO:0035024), cell development (GO:0048468), animal organ development (GO:0048513), negative regulation of stress fiber assembly (GO:0051497), establishment of skin barrier (GO:0061436), negative regulation of thrombin-activated receptor signaling pathway (GO:0070495), negative regulation of guanyl-nucleotide exchange factor activity (GO:1905098)

GO Molecular Function (13): protein tyrosine kinase activity (GO:0004713), hepatocyte growth factor receptor activity (GO:0005008), ATP binding (GO:0005524), semaphorin receptor activity (GO:0017154), protein phosphatase binding (GO:0019903), identical protein binding (GO:0042802), molecular function activator activity (GO:0140677), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), transmembrane receptor protein tyrosine kinase activity (GO:0004714), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): extracellular region (GO:0005576), plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), cell surface (GO:0009986), membrane (GO:0016020), signaling receptor complex (GO:0043235), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Signaling by MET	7
MET promotes cell motility	3
Intracellular signaling by second messengers	1
PI3K/AKT Signaling in Cancer	1
Sema4D in semaphorin signaling	1
MAPK1/MAPK3 signaling	1
Negative regulation of the PI3K/AKT network	1
Listeria monocytogenes entry into host cells	1
Transcriptional Regulation by MECP2	1
Negative regulation of MET activity	1
MITF-M-dependent gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
endothelial cell development	1
epithelial cell morphogenesis	1
gland development	1
hepaticobiliary system development	1
signal transduction	1
enzyme-linked receptor protein signaling pathway	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
cell differentiation	1
generation of neurons	1
animal organ development	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
tube morphogenesis	1
epithelial tube morphogenesis	1
morphogenesis of a branching epithelium	1
chemotaxis	1
regulation of postsynaptic membrane potential	1
chemical synaptic transmission, postsynaptic	1
cell surface receptor signaling pathway	1
hydrogen peroxide-mediated programmed cell death	1
negative regulation of programmed cell death	1
regulation of hydrogen peroxide-mediated programmed cell death	1
positive regulation of endothelial cell migration	1
endothelial cell chemotaxis	1
positive regulation of chemotaxis	1
regulation of endothelial cell chemotaxis	1
phosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
gene expression	1
regulation of macromolecule biosynthetic process	1

Protein interactions and networks

STRING

5090 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MET	HGF	P14210	999
MET	CD44	P16070	991
MET	GRB2	P29354	980
MET	EGFR	P00533	979
MET	STAT3	P40763	948
MET	CDH1	P12830	944
MET	IL32	P24001	921
MET	S100A8	P05109	920
MET	CXCL12	P48061	902
MET	PLXNB1	O43157	899
MET	SHC1	P29353	883
MET	CBL	P22681	874
MET	EGF	P01133	852
MET	IL6	P05231	852
MET	PTPN11	Q06124	810

IntAct

362 interactions, top by confidence:

A	B	Type	Score
ERBB3	ERBB2	psi-mi:“MI:0914”(association)	0.970
CBL	MET	psi-mi:“MI:2364”(proximity)	0.860
CBL	MET	psi-mi:“MI:0407”(direct interaction)	0.860
MET	CBL	psi-mi:“MI:0915”(physical association)	0.860
CBL	MET	psi-mi:“MI:0915”(physical association)	0.860
MET	CBL	psi-mi:“MI:0220”(ubiquitination reaction)	0.860
HGF	MET	psi-mi:“MI:0407”(direct interaction)	0.850
MET	HGF	psi-mi:“MI:0407”(direct interaction)	0.850
MET	HGF	psi-mi:“MI:0915”(physical association)	0.850
EGFR	MET	psi-mi:“MI:0217”(phosphorylation reaction)	0.800
MET	EGFR	psi-mi:“MI:0915”(physical association)	0.800
EGFR	MET	psi-mi:“MI:0915”(physical association)	0.800
EGFR	MET	psi-mi:“MI:0914”(association)	0.800
MET	EGFR	psi-mi:“MI:0914”(association)	0.800

BioGRID (371): MET (Far Western), MET (Two-hybrid), MET (Affinity Capture-MS), MET (Affinity Capture-MS), MET (Affinity Capture-MS), MET (Co-localization), MET (Co-localization), SOCS1 (Affinity Capture-Western), MET (Affinity Capture-Western), MET (Reconstituted Complex), MET (Affinity Capture-Western), MET (Affinity Capture-Western), MET (Affinity Capture-MS), EGFR (Affinity Capture-Western), ERBB3 (Affinity Capture-Western)

ESM2 similar proteins: A0A1B0GTW7, A0A1D5NSK0, A0A1L8HYT7, A0A286YEC0, A0M8R7, A0M8S8, A1X150, E2RK30, O60486, O62446, P08581, P08F94, P10643, P16056, P97523, Q00PJ8, Q07DV8, Q07DY1, Q07DZ1, Q07E01, Q07E24, Q07E37, Q07E48, Q09YH7, Q09YI9, Q09YK0, Q09YL1, Q09YN5, Q108U6, Q2IBA6, Q2IBC0, Q2IBD8, Q2IBF2, Q2IBG7, Q2QL89, Q2QLA9, Q2QLC0, Q2QLE0, Q2QLF1, Q2QLG5

Diamond homologs: A0JM20, A0M8R7, A0M8S8, A1X150, F1QVU0, G3V9H8, O02466, O35346, P00519, P00520, P00521, P00522, P00529, P06213, P07949, P08069, P08581, P08941, P09760, P0DV84, P10447, P13368, P14617, P16056, P20806, P22182, P23049, P30530, P33497, P34152, P34925, P35546, P35590, P42684, P55144, P55146, P57097, P70451, P97523, P97793

SIGNOR signaling

79 interactions.

A	Effect	B	Mechanism
MET	down-regulates	GLMN	relocalization
PTPRB	down-regulates	MET	dephosphorylation
PTPN1	down-regulates	MET	dephosphorylation
MET	up-regulates	PTK2	phosphorylation
N1’-[3-fluoro-4-[[6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinolinyl]oxy]phenyl]-N1-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	down-regulates	MET	“chemical inhibition”
PTPN2	down-regulates	MET	dephosphorylation
CBL	“down-regulates quantity by destabilization”	MET	ubiquitination
AMG-208	down-regulates	MET	“chemical inhibition”
“AMG 458”	down-regulates	MET	“chemical inhibition”
LSM-1131	down-regulates	MET	“chemical inhibition”
N-[4-[(2-amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-2-oxo-3-pyridinecarboxamide	down-regulates	MET	“chemical inhibition”
“BMS 794833”	down-regulates	MET	“chemical inhibition”
crizotinib	down-regulates	MET	“chemical inhibition”
6-[difluoro-[6-(1-methyl-4-pyrazolyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl]quinoline	down-regulates	MET	“chemical inhibition”
N-[[3-fluoro-4-[[2-(1-methyl-4-imidazolyl)-7-thieno[3,2-b]pyridinyl]oxy]anilino]-sulfanylidenemethyl]-2-phenylacetamide	down-regulates	MET	“chemical inhibition”
MK-2461	down-regulates	MET	“chemical inhibition”
NVP-BVU972	down-regulates	MET	“chemical inhibition”
2-[4-[3-(6-quinolinylmethyl)-5-triazolo[4,5-b]pyrazinyl]-1-pyrazolyl]ethanol	down-regulates	MET	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 119 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	8	69.6×	1e-11
Signaling by ERBB2 ECD mutants	8	65.5×	2e-11
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	8	55.7×	6e-11
PI3K events in ERBB2 signaling	6	49.1×	7e-08
Signaling by ERBB2 KD Mutants	9	46.4×	2e-11
GAB1 signalosome	6	46.4×	9e-08
Signaling by FLT3 ITD and TKD mutants	5	46.4×	1e-06
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	7	44.3×	7e-09

GO biological processes:

GO term	Partners	Fold	FDR
Schwann cell development	6	62.0×	1e-07
negative regulation of epidermal growth factor receptor signaling pathway	5	37.5×	2e-05
epidermal growth factor receptor signaling pathway	11	26.7×	2e-10
negative regulation of cell adhesion	7	26.3×	2e-06
B cell receptor signaling pathway	6	23.6×	2e-05
semaphorin-plexin signaling pathway	6	23.6×	2e-05
insulin receptor signaling pathway	9	19.6×	2e-07
T cell differentiation	5	18.8×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

4867 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	2
Uncertain significance	2659
Likely benign	1152
Benign	131

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
13882	NM_000245.4(MET):c.3562G>T (p.Val1188Leu)	Pathogenic
13884	NM_000245.4(MET):c.3682G>A (p.Asp1228Asn)	Pathogenic
13889	NM_000245.4(MET):c.3750G>A (p.Met1250Ile)	Pathogenic
13890	NM_000245.4(MET):c.3731A>G (p.Lys1244Arg)	Pathogenic
183686	NM_000245.4(MET):c.2521T>G (p.Phe841Val)	Pathogenic
998144	NM_000245.4(MET):c.2855del (p.Phe952fs)	Pathogenic
3384110	NM_000245.4(MET):c.3503T>G (p.Phe1168Cys)	Likely pathogenic
376126	NM_000245.4(MET):c.3749T>C (p.Met1250Thr)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

9195 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:116775106:G:A	G1085E	1.000
7:116775111:G:A	G1087R	1.000
7:116775111:G:C	G1087R	1.000
7:116775111:G:T	G1087W	1.000
7:116777389:G:A	G1087E	1.000
7:116777394:T:A	F1089I	1.000
7:116777394:T:C	F1089L	1.000
7:116777394:T:G	F1089V	1.000
7:116777395:T:C	F1089S	1.000
7:116777395:T:G	F1089C	1.000
7:116777396:T:A	F1089L	1.000
7:116777396:T:G	F1089L	1.000
7:116777397:G:C	G1090R	1.000
7:116777398:G:A	G1090D	1.000
7:116777412:G:A	G1095R	1.000
7:116777412:G:C	G1095R	1.000
7:116777412:G:T	G1095W	1.000
7:116777413:G:A	G1095E	1.000
7:116777450:T:G	C1107W	1.000
7:116777452:C:A	A1108D	1.000
7:116777457:A:C	K1110Q	1.000
7:116777457:A:G	K1110E	1.000
7:116777458:A:T	K1110I	1.000
7:116777459:A:C	K1110N	1.000
7:116777459:A:T	K1110N	1.000
7:116777464:T:C	L1112S	1.000
7:116778805:T:C	F1124L	1.000
7:116778806:T:C	F1124S	1.000
7:116778807:T:A	F1124L	1.000
7:116778807:T:G	F1124L	1.000

dbSNP variants (sampled 300 via entrez): RS1000009944 (7:116743985 G>A), RS1000044357 (7:116789399 T>C), RS1000047140 (7:116774450 G>A,T), RS1000053326 (7:116757014 A>C), RS1000070601 (7:116706843 C>T), RS1000114390 (7:116787820 G>A,C,T), RS1000183177 (7:116682929 A>T), RS1000206092 (7:116785195 C>T), RS1000211667 (7:116716493 GAAAGAAAGAA>G), RS1000216862 (7:116737923 G>A,C), RS1000238085 (7:116762048 A>C,G), RS1000278836 (7:116770593 C>T), RS1000279027 (7:116778442 A>C,G), RS1000302339 (7:116764491 G>T), RS1000317282 (7:116706495 G>A)

Disease associations

OMIM: gene MIM:164860 | disease phenotypes: MIM:616705, MIM:114550, MIM:607278, MIM:609143, MIM:620019, MIM:167000, MIM:605074, MIM:142340, MIM:236000, MIM:108120, MIM:114500

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary papillary renal cell carcinoma	Definitive	Autosomal dominant
papillary renal cell carcinoma	Definitive	Autosomal dominant
autosomal recessive nonsyndromic hearing loss 97	Strong	Autosomal recessive
osteofibrous dysplasia	Supportive	Autosomal dominant
hearing loss, autosomal recessive	Supportive	Autosomal recessive
arthrogryposis, distal, IIa 11	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (3)

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

Disease	Classification	Inheritance
papillary renal cell carcinoma	Definitive	AD
complex neurodevelopmental disorder	Disputed	AD
nonsyndromic genetic hearing loss	Limited	AR

Mondo (24): renal cell carcinoma (MONDO:0005086), hereditary neoplastic syndrome (MONDO:0015356), autosomal recessive nonsyndromic hearing loss 97 (MONDO:0014739), hepatocellular carcinoma (MONDO:0007256), osteofibrous dysplasia (MONDO:0011806), arthrogryposis, distal, IIa 11 (MONDO:0031045), ovarian cancer (MONDO:0008170), lymphedema (MONDO:0019297), breast carcinoma (MONDO:0004989), squamous cell lung carcinoma (MONDO:0005097), intellectual disability (MONDO:0001071), hereditary papillary renal cell carcinoma (MONDO:0003789), pediatric hepatocellular carcinoma (MONDO:0018055), nonsyndromic genetic hearing loss (MONDO:0019497), hepatoblastoma (MONDO:0018666)

Orphanet (17): Inherited cancer-predisposing syndrome (Orphanet:140162), Renal cell carcinoma (Orphanet:217071), Hereditary papillary renal cell carcinoma (Orphanet:47044), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Osteofibrous dysplasia (Orphanet:488265), Hepatocellular carcinoma (Orphanet:88673), Rare ovarian cancer (Orphanet:213500), Pediatric hepatocellular carcinoma (Orphanet:33402), Rare non-syndromic genetic deafness (Orphanet:87884), Hepatoblastoma (Orphanet:449), Congenital diaphragmatic hernia (Orphanet:2140), Classic Hodgkin lymphoma (Orphanet:391), Neuroblastoma (Orphanet:635), Distal arthrogryposis type 1 (Orphanet:1146), OBSOLETE: Lymphedema (Orphanet:79383)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0005584	Renal cell carcinoma
HP:0003002	Breast carcinoma

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST000266_1	Multiple sclerosis (severity)	6.000000e-06
GCST002216_16	Triglycerides	2.000000e-08
GCST002456_5	PR segment duration	5.000000e-12
GCST003818_64	Resting heart rate	7.000000e-09
GCST004003_2	Hematocrit	2.000000e-06
GCST004232_29	HDL cholesterol levels	2.000000e-26
GCST004234_4	HDL cholesterol levels	6.000000e-27
GCST004237_15	Triglyceride levels	5.000000e-09
GCST004237_36	Triglyceride levels	8.000000e-18
GCST004238_7	Triglyceride levels	3.000000e-18
GCST005789_14	Resting heart rate	7.000000e-06
GCST005956_17	Waist-to-hip ratio adjusted for BMI	5.000000e-09
GCST005962_49	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-07
GCST006019_32	Gamma glutamyl transferase levels	5.000000e-09
GCST006585_2690	Blood protein levels	1.000000e-06
GCST006585_665	Blood protein levels	3.000000e-06
GCST007269_219	Pulse pressure	3.000000e-08
GCST007431_5	Lung function (FEV1/FVC)	4.000000e-12
GCST007927_27	Medication use (beta blocking agents)	4.000000e-08
GCST011349_10	Gamma glutamyl transferase levels	1.000000e-09
GCST012489_137	Heel bone mineral density x serum urate levels interaction	2.000000e-08
GCST90000047_144	Age at first sexual intercourse	4.000000e-10
GCST90011898_146	Alanine aminotransferase levels	1.000000e-09

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0005095	PR segment
EFO:0004348	hematocrit
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0005763	pulse pressure measurement
EFO:0004713	FEV/FVC ratio
EFO:0009929	Beta blocking agent use measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (13)

Descriptor	Name	Tree numbers
D006528	Carcinoma, Hepatocellular	C04.557.470.200.025.255; C04.588.274.623.160; C06.301.623.160; C06.552.697.160
D002292	Carcinoma, Renal Cell	C04.557.470.200.025.390; C04.588.945.947.535.160; C12.050.351.937.820.535.160; C12.050.351.968.419.473.160; C12.200.758.820.750.160; C12.200.777.419.473.160; C12.900.820.535.160; C12.950.419.473.160; C12.950.983.535.160
D018197	Hepatoblastoma	C04.557.435.380
D065630	Hernias, Diaphragmatic, Congenital	C16.131.433; C23.300.707.960.500.116
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008209	Lymphedema	C15.604.496
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D009447	Neuroblastoma	C04.557.465.625.600.590.650.550; C04.557.470.670.590.650.550; C04.557.580.625.600.590.650.550
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
C564609	Deafness, Autosomal Recessive (supp.)
C580334	Nonsyndromic Deafness (supp.)
C563276	Osteofibrous Dysplasia (supp.)
C563787	Tibia, Bowing of, with Pseudarthrosis and Pectus Excavatum (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3717 (SINGLE PROTEIN), CHEMBL6195521 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195562 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

95 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 256,286 (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
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289494	TIVOZANIB	4	4,455
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	285
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2103868	CABOZANTINIB S-MALATE	4	3,179
CHEMBL2105712	AFATINIB DIMALEATE	4	3,215
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3188267	CAPMATINIB	4	2,884
CHEMBL3402762	TEPOTINIB	4	1,276
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL4113131	ENSARTINIB	4
CHEMBL477772	PAZOPANIB	4
CHEMBL502835	NINTEDANIB	4
CHEMBL535	SUNITINIB	4
CHEMBL553	ERLOTINIB	4
CHEMBL601719	CRIZOTINIB	4
CHEMBL608533	MIDOSTAURIN	4
CHEMBL939	GEFITINIB	4
CHEMBL1091644	LINSITINIB	3
CHEMBL1241855	RIGOSERTIB	3

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

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs40239	MET		0.00	0
rs2237717	MET		0.00	0
rs11762213	MET		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type X RTKs: HGF (hepatocyte growth factor) receptor family

Most potent curated ligand interactions (44 total), top 25:

Ligand	Action	Affinity	Parameter
amivantamab	Binding	10.4	pKd
emibetuzumab	Binding	10.0	pKd
capmatinib	Inhibition	9.89	pIC50
vilzemetkib	Inhibition	9.76	pIC50
SGX-523	Inhibition	9.72	pKd
telisotuzumab vedotin	Binding	9.66	pEC50
gumarontinib	Inhibition	9.38	pIC50
ensartinib	Inhibition	9.13	pIC50
elzovantinib	Inhibition	9.12	pIC50
cabozantinib	Inhibition	8.9	pIC50
foretinib	Inhibition	8.85	pKd
crizotinib	Inhibition	8.7	pKi
MK-2461	Inhibition	8.6	pIC50
altiratinib	Inhibition	8.57	pIC50
dalmelitinib	Inhibition	8.54	pIC50
D6808	Inhibition	8.54	pIC50
vabametkib	Inhibition	8.52	pIC50
tepotinib	Inhibition	8.52	pIC50
GE-137	Binding	8.52	pKd
BMS-777607	Inhibition	8.41	pIC50
PHA-665752	Inhibition	8.4	pKi
onartuzumab	Binding	8.37	pIC50
merestinib	Inhibition	8.33	pIC50
AMG-337	Inhibition	8.3	pIC50
savolitinib	Inhibition	8.3	pIC50

Binding affinities (BindingDB)

995 measured of 1804 human assays (1804 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[[6-(3,5-difluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl]-7-[2-(1,2,4-triazol-1-yl)ethoxy]-1,5-naphthyridin-4-amine	KI	0.1 nM	US-9066954: Fused heterocyclic derivatives and methods of use
(E)-N1-(3-fluoro-4-(6-methoxy-7-(3-(piperidin-1-yl)propoxy)quinoline-4-yloxy)phenyl)-N4-(propiophenone)thiosemicarbazone	IC50	0.2 nM	US-9783499: Quinoline derivatives and their applications
[(E)-1-[3-[(1S)-1-quinolin-6-ylethyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]ethylideneamino]urea	IC50	0.2 nM	US-8497368: Heterocyclic hydrazone compounds
[(Z)-[amino-[3-(quinolin-6-ylmethyl)triazolo[4,5-b]pyrazin-5-yl]methylidene]amino]urea	IC50	0.2 nM	US-8497368: Heterocyclic hydrazone compounds
[(E)-1-[3-[(7-fluoroquinolin-6-yl)methyl]triazolo[4,5-b]pyrazin-5-yl]ethylideneamino]urea	IC50	0.2 nM	US-8497368: Heterocyclic hydrazone compounds
N-[4-[[2-(cyclopropanecarbonylamino)-4-pyridinyl]oxy]phenyl]-1,5-dimethyl-3-oxo-2-phenylpyrazole-4-carboxamide	KD	0.21 nM	US-8975282: Substituted pyrazolone compounds and methods of use
4-[[8-fluoro-6-(4-methylthiophen-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]methoxy]-7-methoxyquinoline	KI	0.3 nM	US-9066954: Fused heterocyclic derivatives and methods of use
[(E)-1-[3-[(5,7-difluoroquinolin-6-yl)methyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]ethylideneamino]urea	IC50	0.3 nM	US-8497368: Heterocyclic hydrazone compounds
[(E)-[3-(quinolin-6-ylmethyl)triazolo[4,5-b]pyrazin-5-yl]methylideneamino]urea	IC50	0.3 nM	US-8497368: Heterocyclic hydrazone compounds
5,7-difluoro-6-[[6-(1-nitrosoethyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl]quinoline	IC50	0.4 nM	US-8507676: Heterocyclic oxime compounds
[(E)-1-[3-[(5,7-difluoroquinolin-6-yl)methyl]imidazo[1,2-b]pyridazin-6-yl]ethylideneamino]urea	IC50	0.4 nM	US-8497368: Heterocyclic hydrazone compounds
[(E)-1-[3-[(1S)-1-quinolin-6-ylethyl]imidazo[1,2-b]pyridazin-6-yl]ethylideneamino]urea	IC50	0.4 nM	US-8497368: Heterocyclic hydrazone compounds
N-[(E)-1-[3-[(7-fluoroquinolin-6-yl)methyl]triazolo[4,5-b]pyrazin-5-yl]ethylideneamino]acetamide	IC50	0.4 nM	US-8497368: Heterocyclic hydrazone compounds
[(E)-1-[3-[(1R)-1-(5,7-difluoroquinolin-6-yl)ethyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]ethylideneamino] carbamate	IC50	0.48 nM	US-8507676: Heterocyclic oxime compounds
N-[4-[[2-(cyclopropanecarbonylamino)-4-pyridinyl]oxy]-3-fluorophenyl]-1,5-dimethyl-3-oxo-2-phenylpyrazole-4-carboxamide	KD	0.5 nM	US-8975282: Substituted pyrazolone compounds and methods of use
[(E)-1-[3-[1-(5,7-difluoroquinolin-6-yl)ethyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]ethylideneamino]urea	IC50	0.5 nM	US-8497368: Heterocyclic hydrazone compounds
N-[(E)-1-[3-[(7-fluoroquinolin-6-yl)methyl]triazolo[4,5-b]pyrazin-5-yl]ethylideneamino]pyridine-4-carboxamide	IC50	0.5 nM	US-8497368: Heterocyclic hydrazone compounds
2-fluoro-N-[(2R)-2-hydroxypropyl]-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide	IC50	0.55 nM	US-9221824: Imidazo[1,2-B][1,2,4]triazines as c-Met inhibitors
2-chloro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide	IC50	0.55 nM	US-9221824: Imidazo[1,2-B][1,2,4]triazines as c-Met inhibitors
2-chloro-N-[(1S)-1-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl]-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide	IC50	0.55 nM	US-9221824: Imidazo[1,2-B][1,2,4]triazines as c-Met inhibitors
N-methyl-5-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]pyridine-2-carboxamide	IC50	0.55 nM	US-9221824: Imidazo[1,2-B][1,2,4]triazines as c-Met inhibitors
N,2-dimethyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide	IC50	0.55 nM	US-9221824: Imidazo[1,2-B][1,2,4]triazines as c-Met inhibitors
6-[[6-(4-methylthiophen-2-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl]quinoline	KI	0.7 nM	US-9066954: Fused heterocyclic derivatives and methods of use
[(E)-1-[3-[difluoro(quinolin-6-yl)methyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]ethylideneamino]urea	IC50	0.7 nM	US-8497368: Heterocyclic hydrazone compounds
1-methyl-1-[(E)-1-[3-(quinolin-6-ylmethyl)triazolo[4,5-b]pyrazin-5-yl]ethylideneamino]urea	IC50	0.8 nM	US-8497368: Heterocyclic hydrazone compounds
7-methoxy-N-[(6-phenyl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-3-yl)methyl]-1,5-naphthyridin-4-amine	KI	0.9 nM	US-9066954: Fused heterocyclic derivatives and methods of use
3-[(E)-1-[3-[(7-fluoroquinolin-6-yl)methyl]triazolo[4,5-b]pyrazin-5-yl]ethylideneamino]-5-hydroxy-1H-imidazol-2-one	IC50	0.9 nM	US-8497368: Heterocyclic hydrazone compounds
2,6-dimethyl-4-[3-(2-propan-2-yloxyethoxy)-1H-indazol-5-yl]-3,4-dihydropyridine-3,5-dicarbonitrile	IC50	1 nM	US-8551989: Substituted 4-(indazolyl)-1,4-dihydropyridines and methods of use thereof
3-isocyano-2-methyl-4-(3-methyl-2H-indazol-5-yl)-4,7-dihydro-3H-furo[3,4-b]pyridin-5-one	IC50	1 nM	US-8759341: Bi- and tricyclic indazole-substituted 1,4-dihydropyridine derivatives and uses thereof
6-[[8-fluoro-6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-N-(1-methylpiperidin-4-yl)quinolin-3-amine	IC50	1 nM	US-9062045: Triazolopyridine compounds
(3S)-1-[6-[[8-fluoro-6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-yl]-N,N-dimethylpyrrolidin-3-amine	IC50	1 nM	US-9062045: Triazolopyridine compounds
3-[(3S,5R)-3,5-dimethylpiperazin-1-yl]-6-[[8-fluoro-6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinoline	IC50	1 nM	US-9062045: Triazolopyridine compounds
6-[[8-fluoro-6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-3-(4-methoxypiperidin-1-yl)quinoline	IC50	1 nM	US-9062045: Triazolopyridine compounds
2-[[6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-yl]amino]ethanol	IC50	1 nM	US-9062045: Triazolopyridine compounds
3-(4,4-difluoropiperidin-1-yl)-6-[[8-fluoro-6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinoline	IC50	1 nM	US-9062045: Triazolopyridine compounds
US9073939, 3	IC50	1 nM	US-9073939: Indazolyl-substituted dihydroisoxa-zolopyridines and methods of use thereof
2-fluoro-5-[3-[[4-[5-[1-(2-hydroxyethyl)pyrazol-4-yl]pyrimidin-2-yl]morpholin-2-yl]methyl]triazolo[4,5-b]pyrazin-5-yl]benzonitrile	IC50	1 nM	US-9403831: Triazolopyrazine derivative and use thereof
2-methyl-4-(3-methyl-2H-indazol-5-yl)-6-(trifluoromethyl)-1,4-dihydropyridine-3,5-dicarbonitrile	IC50	1 nM	US-9422263: Fluoro-substituted 3,5-dicyano-4-(1H-indazol-5-yl)-2,6-dimethyl-1,4-dihydropyridine derivatives and methods of use thereof
N-{3-fluoro-4-[(7-methoxyquinolin-4-yl)oxy]phenyl}-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide	KI	1 nM
N-{3-fluoro-4-[(7-methoxyquinolin-4-yl)oxy]phenyl}-1-[(2R)-2-hydroxypropyl]-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide	KI	1 nM
2-chloro-4-(3-{[(7-methoxyquinolin-4-yl)oxy]methyl}-[1,2,4]triazolo[4,3-a]pyridazin-6-yl)-N-methylbenzamide	IC50	1 nM
7-methoxy-4-{[6-(4-methylthiophen-2-yl)-[1,2,4]triazolo[4,3-a]pyridazin-3-yl]methoxy}quinoline	IC50	1 nM
N-{4-[(2-amino-3-ethynylpyridin-4-yl)oxy]-3-fluorophenyl}-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide	IC50	1 nM
N-{4-[(2-amino-3-chloropyridin-4-yl)oxy]-3-fluorophenyl}-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide	IC50	1 nM
[(E)-1-[3-[(7-fluoroquinolin-6-yl)methyl]imidazo[1,2-b]pyridazin-6-yl]ethylideneamino]urea	IC50	1 nM	US-8497368: Heterocyclic hydrazone compounds
1-[(E)-1-[3-[(7-fluoroquinolin-6-yl)methyl]imidazo[1,2-b]pyridazin-6-yl]ethylideneamino]-1-methylurea	IC50	1 nM	US-8497368: Heterocyclic hydrazone compounds
1-[(E)-1-[3-[(7-fluoroquinolin-6-yl)methyl]imidazo[1,2-b]pyridazin-6-yl]ethylideneamino]imidazolidine-2,4-dione	IC50	1 nM	US-8497368: Heterocyclic hydrazone compounds
[(E)-1-[3-(quinolin-6-ylmethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]ethylideneamino]urea	IC50	1 nM	US-8497368: Heterocyclic hydrazone compounds
3-[(E)-1-[3-[(5,7-difluoroquinolin-6-yl)methyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]ethylideneamino]-1,3-oxazolidin-2-one	IC50	1 nM	US-8497368: Heterocyclic hydrazone compounds
methyl N-[(E)-1-[3-[(7-fluoroquinolin-6-yl)methyl]triazolo[4,5-b]pyrazin-5-yl]ethylideneamino]carbamate	IC50	1 nM	US-8497368: Heterocyclic hydrazone compounds

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.72	IC50	0.019	nM	CHEMBL5184459
10.46	IC50	0.035	nM	CHEMBL5174958
10.00	Ki	0.1	nM	CHEMBL3668200
9.92	IC50	0.12	nM	CHEMBL3797911
9.89	IC50	0.13	nM	CHEMBL3582305
9.89	IC50	0.13	nM	CAPMATINIB
9.85	IC50	0.14	nM	ELZOVANTINIB
9.72	IC50	0.19	nM	CHEMBL3797911
9.72	IC50	0.19	nM	CHEMBL6133512
9.72	Kd	0.19	nM	SGX-523
9.70	IC50	0.2	nM	CHEMBL2032280
9.70	Kd	0.2	nM	CRIZOTINIB
9.70	IC50	0.2	nM	CHEMBL3674521
9.70	IC50	0.2	nM	CHEMBL3674540
9.70	IC50	0.2	nM	CHEMBL3674547
9.70	IC50	0.2	nM	CHEMBL5832315
9.70	IC50	0.2	nM	CHEMBL6188807
9.70	IC50	0.2	nM	CHEMBL1802904
9.68	Kd	0.21	nM	CHEMBL3703197
9.66	IC50	0.22	nM	CHEMBL5286745
9.62	IC50	0.24	nM	CHEMBL3797579
9.59	IC50	0.26	nM	CHEMBL5565127
9.59	IC50	0.26	nM	CHEMBL6168943
9.57	Kd	0.27	nM	PHA-665752
9.52	IC50	0.3	nM	CHEMBL3674515
9.52	IC50	0.3	nM	CHEMBL3674541
9.52	Ki	0.3	nM	CHEMBL3668185
9.52	Kd	0.3	nM	CAPMATINIB
9.52	IC50	0.3	nM	CHEMBL4061378
9.52	IC50	0.3	nM	CHEMBL4104884
9.52	EC50	0.3	nM	PF-04217903
9.49	IC50	0.32	nM	CHEMBL2376640
9.48	IC50	0.33	nM	CHEMBL6152766
9.41	IC50	0.39	nM	CHEMBL6164718
9.40	Ki	0.4	nM	CHEMBL2032026
9.40	IC50	0.4	nM	FORETINIB
9.40	IC50	0.4	nM	MK-2461
9.40	IC50	0.4	nM	CHEMBL3674495
9.40	IC50	0.4	nM	CHEMBL3674505
9.40	IC50	0.4	nM	CHEMBL3674548
9.40	IC50	0.4	nM	CHEMBL3651418
9.40	IC50	0.4	nM	CAPMATINIB
9.40	IC50	0.4	nM	CHEMBL4097173
9.40	IC50	0.4	nM	CHEMBL4070258
9.38	IC50	0.42	nM	CHEMBL3800471
9.37	IC50	0.43	nM	CHEMBL3800420
9.36	IC50	0.44	nM	CHEMBL4214018
9.35	IC50	0.45	nM	CHEMBL5575349
9.34	IC50	0.46	nM	CHEMBL3797579
9.34	IC50	0.46	nM	CHEMBL3797914

PubChem BioAssay actives

3371 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[[4-[5-(1-piperidin-4-ylpyrazol-4-yl)pyrimidin-2-yl]morpholin-2-yl]methyl]-6-pyridin-3-ylpyridazin-3-one	1849624: Inhibition of human recombinant c-MET in presence of ATP by HTRF assay	ic50	<0.0001	uM
2-fluoro-N-methyl-4-[3-(quinolin-6-ylmethyl)-[1,2,4]triazolo[4,3-b][1,2,4]triazin-6-yl]benzamide	1229108: Inhibition of C-Met (unknown origin) using polu (Glu,Tyr)4:1 substrate after 30 mins incubation by multi-well spectrophotometry	ic50	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	2003522: Inhibition of MET (unknown origin)	ic50	0.0001	uM
Capmatinib	1276952: Inhibition of c-Met (unknown origin)	ic50	0.0001	uM
Crizotinib	1337142: Binding affinity to MET (unknown origin)	kd	0.0002	uM
6-[difluoro-[6-(4-fluorophenyl)-[1,2,4]triazolo[4,3-b][1,2,4]triazin-3-yl]methyl]quinoline	1297781: Inhibition of recombinant c-Met (unknown origin) using poly (Glu, Tyr) 4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0002	uM
1-(2-morpholin-4-ylethyl)-3-[6-[(6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)sulfanyl]-1,3-benzothiazol-2-yl]urea	1942584: Inhibition of human MET H1094Y mutant incubated for 1 hrs by ELISA assay	ic50	0.0002	uM
6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulfanyl]quinoline	624794: Binding constant for MET kinase domain	kd	0.0002	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	624794: Binding constant for MET kinase domain	kd	0.0003	uM
3-(1-methylpyrazol-4-yl)-6-[1-(5-pyridin-4-yltriazolo[4,5-b]pyrazin-3-yl)ethyl]quinoline	1466273: Inhibition of c-MET (unknown origin) using TK substrate-biotin peptide as substrate preincubated for 5 to 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ic50	0.0003	uM
4-[3-[1-[5,7-difluoro-3-(1-methylpyrazol-4-yl)quinolin-6-yl]ethyl]triazolo[4,5-b]pyrazin-5-yl]-2-fluorobenzamide	1466273: Inhibition of c-MET (unknown origin) using TK substrate-biotin peptide as substrate preincubated for 5 to 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ic50	0.0003	uM
N-[3-fluoro-4-[6-methoxy-7-(prop-2-enoylamino)naphthalen-1-yl]oxyphenyl]-2,3-dimethyl-5-oxo-4-phenylpyrazole-1-carboxamide	2096125: Inhibition of N-terminal GST tagged human recombinant c-Met (956 to end residues) expressed in baculovirus infected Sf9 cells using Poly (4:1 Glu, Tyr) as substrate incubated for 60 mins in presence of ATP by ADP-Glo luminescent assay	ic50	0.0003	uM
2-[4-[3-(quinolin-6-ylmethyl)triazolo[4,5-b]pyrazin-5-yl]pyrazol-1-yl]ethanol	1636783: Inhibition of c-Met kinase (unknown origin) assessed as decrease in phosphorylation of TK substrate-biotin peptide preincubated for 5 to 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ec50	0.0003	uM
1-(2-hydroxyethyl)-N-[5-(7-methoxyquinolin-4-yl)oxy-2-pyridinyl]-5-methyl-3-oxo-2-phenylpyrazole-4-carboxamide	662095: Inhibition of c-Met by HTRF assay	ki	0.0004	uM
3-[3-(quinolin-6-ylmethyl)-[1,2,4]triazolo[4,3-b][1,2,4]triazin-6-yl]phenol	1297781: Inhibition of recombinant c-Met (unknown origin) using poly (Glu, Tyr) 4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0004	uM
2-[4-[3-[1-[5,7-difluoro-3-(1-methylpyrazol-4-yl)quinolin-6-yl]ethyl]triazolo[4,5-b]pyrazin-5-yl]pyrazol-1-yl]ethanol	1466273: Inhibition of c-MET (unknown origin) using TK substrate-biotin peptide as substrate preincubated for 5 to 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ic50	0.0004	uM
5,7-difluoro-3-(1-methylpyrazol-4-yl)-6-[1-[5-(1-methylpyrazol-4-yl)triazolo[4,5-b]pyrazin-3-yl]ethyl]quinoline	1466273: Inhibition of c-MET (unknown origin) using TK substrate-biotin peptide as substrate preincubated for 5 to 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ic50	0.0004	uM
N-(2-aminophenyl)-4-[[4-[2-[3-(1-methylpyrazol-4-yl)-6-oxopyridazin-1-yl]ethoxy]quinolin-7-yl]oxymethyl]benzamide	1379286: Inhibition of recombinant human His-tagged c-Met cytoplasmic domain (956 to 1390 residues) expressed in baculovirus expression system using poly (Glu,Tyr)4:1 as substrate after 60 mins by spectrophotometric analysis	ic50	0.0004	uM
6-[3-[difluoro(quinolin-6-yl)methyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]-1-[2-oxo-2-(4-propan-2-ylpiperazin-1-yl)ethyl]-3,4-dihydroquinolin-2-one	2088142: Inhibition of c-Met (unknown origin) preincubated for 10 mins followed by substrate and ATP addition measured after 50 mins by fluorescence based microtiter-plate reader analysis	ic50	0.0004	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	1142763: Inhibition of c-Met (unknown origin)	ic50	0.0004	uM
14-[[[(2R)-1,4-dioxan-2-yl]methyl-methylsulfamoyl]amino]-5-(1-methylpyrazol-4-yl)-2-oxo-7-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,9,12,14-heptaene	1276952: Inhibition of c-Met (unknown origin)	ic50	0.0004	uM
6-(1-methylpyrazol-4-yl)-1-[6-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]sulfonylpyrazolo[4,5-b]pyridine	2003522: Inhibition of MET (unknown origin)	ic50	0.0005	uM
6-[difluoro-[6-(furan-2-yl)-[1,2,4]triazolo[4,3-b][1,2,4]triazin-3-yl]methyl]quinoline	1297781: Inhibition of recombinant c-Met (unknown origin) using poly (Glu, Tyr) 4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0005	uM
2-[4-[3-[1-[7-fluoro-3-(1-methylpyrazol-4-yl)quinolin-6-yl]ethyl]triazolo[4,5-b]pyrazin-5-yl]pyrazol-1-yl]ethanol	1466273: Inhibition of c-MET (unknown origin) using TK substrate-biotin peptide as substrate preincubated for 5 to 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ic50	0.0005	uM
4-bromo-3-[[2-(2,3-dihydro-1-benzofuran-5-yl)acetyl]diazenyl]-2-hydroxy-N-[3-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]propyl]-1H-indole-6-carboxamide	614836: Inhibition of human c-MET	ic50	0.0005	uM
(3Z)-4-bromo-3-[[2-(2,3-dihydro-1-benzofuran-5-yl)acetyl]hydrazinylidene]-N-[4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]butyl]-1,2-dihydroindole-6-carboxamide	1326920: Inhibition of C-Met in human S114 cells assessed as inhibition of HGF-stimulated autophosphorylation preincubated for 60 mins followed by HGF-stimulation measured after 15 minsby DELFIA method	ic50	0.0005	uM
2-[4-[3-[1-[3-(1-methylpyrazol-4-yl)quinolin-6-yl]ethyl]triazolo[4,5-b]pyrazin-5-yl]pyrazol-1-yl]ethanol	1466273: Inhibition of c-MET (unknown origin) using TK substrate-biotin peptide as substrate preincubated for 5 to 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ic50	0.0005	uM
3-(1-methylpyrazol-4-yl)-6-[1-[5-(1-methylpyrazol-4-yl)triazolo[4,5-b]pyrazin-3-yl]ethyl]quinoline	1466273: Inhibition of c-MET (unknown origin) using TK substrate-biotin peptide as substrate preincubated for 5 to 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ic50	0.0005	uM
2-fluoro-N-methyl-4-[3-[1-[3-(1-methylpyrazol-4-yl)quinolin-6-yl]ethyl]triazolo[4,5-b]pyrazin-5-yl]benzamide	1466273: Inhibition of c-MET (unknown origin) using TK substrate-biotin peptide as substrate preincubated for 5 to 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ic50	0.0005	uM
5,7-difluoro-3-(1-methylpyrazol-4-yl)-6-[1-(5-pyridin-4-yltriazolo[4,5-b]pyrazin-3-yl)ethyl]quinoline	1466273: Inhibition of c-MET (unknown origin) using TK substrate-biotin peptide as substrate preincubated for 5 to 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ic50	0.0005	uM
N-hydroxy-7-[4-[2-[3-(1-methylpyrazol-4-yl)-6-oxopyridazin-1-yl]ethoxy]quinolin-7-yl]oxyheptanamide	1379286: Inhibition of recombinant human His-tagged c-Met cytoplasmic domain (956 to 1390 residues) expressed in baculovirus expression system using poly (Glu,Tyr)4:1 as substrate after 60 mins by spectrophotometric analysis	ic50	0.0005	uM
1-(2-hydroxy-2-methylpropyl)-N-[5-(7-methoxyquinolin-4-yl)oxy-2-pyridinyl]-5-methyl-3-oxo-2-phenylpyrazole-4-carboxamide	1798436: HTRF Kinase Inhibition Assay from Article 10.1021/jm800401t: “Discovery of a potent, selective, and orally bioavailable c-Met inhibitor: 1-(2-hydroxy-2-methylpropyl)-N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (AMG 458).”	ki	0.0005	uM
N-[5-(7-methoxyquinolin-4-yl)oxy-2-pyridinyl]-1-methyl-3-oxo-2-phenyl-5-pyridin-4-ylpyrazole-4-carboxamide	662095: Inhibition of c-Met by HTRF assay	ki	0.0006	uM
N-[5-(7-methoxyquinolin-4-yl)oxy-2-pyridinyl]-1-methyl-3-oxo-2-phenyl-5-pyridin-2-ylpyrazole-4-carboxamide	662095: Inhibition of c-Met by HTRF assay	ki	0.0006	uM
6-[[6-(3-methoxyphenyl)-[1,2,4]triazolo[4,3-b][1,2,4]triazin-3-yl]methyl]quinoline	1297781: Inhibition of recombinant c-Met (unknown origin) using poly (Glu, Tyr) 4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0006	uM
2-fluoro-4-[3-[1-[7-fluoro-3-(1-methylpyrazol-4-yl)quinolin-6-yl]ethyl]triazolo[4,5-b]pyrazin-5-yl]benzamide	1466273: Inhibition of c-MET (unknown origin) using TK substrate-biotin peptide as substrate preincubated for 5 to 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ic50	0.0006	uM
(E)-N-(2-aminophenyl)-3-[5-[[4-[2-[3-(1-methylpyrazol-4-yl)-6-oxopyridazin-1-yl]ethoxy]quinolin-7-yl]oxymethyl]-2-pyridinyl]prop-2-enamide	1379286: Inhibition of recombinant human His-tagged c-Met cytoplasmic domain (956 to 1390 residues) expressed in baculovirus expression system using poly (Glu,Tyr)4:1 as substrate after 60 mins by spectrophotometric analysis	ic50	0.0006	uM
N-[4-[(2-amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-1-(4-methoxyphenyl)-2-oxoquinoline-3-carboxamide	1632313: Inhibition of recombinant c-Met (unknown origin) using poly (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA	ic50	0.0006	uM
N-[3-fluoro-4-[6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yl]oxyphenyl]-4-oxo-1-phenylpyridazine-3-carboxamide	1849620: Inhibition of c-MET (unknown origin) using FAM-labelled peptide as substrate incubated for 10 mins in presence of ATP by mobility shift assay	ic50	0.0006	uM
3-[(1S)-1-[3-(2-methoxyethoxy)quinolin-6-yl]ethyl]-5-(3-methyl-1,2-thiazol-5-yl)triazolo[4,5-c]pyridin-4-one	1289769: Inhibition of recombinant MET (unknown origin) using gastrin peptide as substrate preincubated for 30 mins followed by substrate addition incubated for 60 mins by HTRF assay	ic50	0.0006	uM
N-[5-(7-methoxyquinolin-4-yl)oxy-2-pyridinyl]-1-methyl-5-(2-methyl-1,3-thiazol-4-yl)-3-oxo-2-phenylpyrazole-4-carboxamide	662095: Inhibition of c-Met by HTRF assay	ki	0.0007	uM
N-[5-(7-methoxyquinolin-4-yl)oxy-2-pyridinyl]-1-methyl-5-(5-methyl-1,2-oxazol-3-yl)-3-oxo-2-phenylpyrazole-4-carboxamide	662095: Inhibition of c-Met by HTRF assay	ki	0.0007	uM
6-[difluoro-[6-(1-propylpyrazol-4-yl)-[1,2,4]triazolo[4,3-b][1,2,4]triazin-3-yl]methyl]quinoline	1297844: Inhibition of c-Met in human EBC-1 cells assessed as reduction in cell proliferation after 72 hrs by SRB or MTT assay	ic50	0.0007	uM
4-bromo-3-[[2-(2,3-dihydro-1-benzofuran-5-yl)acetyl]diazenyl]-2-hydroxy-N-[3-[(3R)-3-hydroxypyrrolidin-1-yl]propyl]-1H-indole-6-carboxamide	614836: Inhibition of human c-MET	ic50	0.0007	uM
4-bromo-3-[[2-(2,3-dihydro-1-benzofuran-5-yl)acetyl]diazenyl]-2-hydroxy-N-(morpholin-4-ylmethyl)-1H-indole-6-carboxamide	614836: Inhibition of human c-MET	ic50	0.0007	uM
(3Z)-4-bromo-3-[[2-(2,3-dihydro-1-benzofuran-5-yl)acetyl]hydrazinylidene]-N-(2-morpholin-4-ylethyl)-1,2-dihydroindole-6-carboxamide	1326920: Inhibition of C-Met in human S114 cells assessed as inhibition of HGF-stimulated autophosphorylation preincubated for 60 mins followed by HGF-stimulation measured after 15 minsby DELFIA method	ic50	0.0007	uM
(3Z)-4-bromo-3-[[2-(2,3-dihydro-1-benzofuran-5-yl)acetyl]hydrazinylidene]-N-[4-[(3S)-3-hydroxypyrrolidin-1-yl]butyl]-1,2-dihydroindole-6-carboxamide	1326920: Inhibition of C-Met in human S114 cells assessed as inhibition of HGF-stimulated autophosphorylation preincubated for 60 mins followed by HGF-stimulation measured after 15 minsby DELFIA method	ic50	0.0007	uM
7-fluoro-3-(1-methylpyrazol-4-yl)-6-[1-(5-pyridin-4-yltriazolo[4,5-b]pyrazin-3-yl)ethyl]quinoline	1466273: Inhibition of c-MET (unknown origin) using TK substrate-biotin peptide as substrate preincubated for 5 to 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ic50	0.0007	uM
2-fluoro-4-[3-[1-[3-(1-methylpyrazol-4-yl)quinolin-6-yl]ethyl]triazolo[4,5-b]pyrazin-5-yl]benzamide	1466273: Inhibition of c-MET (unknown origin) using TK substrate-biotin peptide as substrate preincubated for 5 to 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ic50	0.0007	uM
7-fluoro-3-(1-methylpyrazol-4-yl)-6-[1-[5-(1-methylpyrazol-4-yl)triazolo[4,5-b]pyrazin-3-yl]ethyl]quinoline	1466273: Inhibition of c-MET (unknown origin) using TK substrate-biotin peptide as substrate preincubated for 5 to 10 mins followed by ATP addition measured after 30 mins by HTRF assay	ic50	0.0007	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Crizotinib	affects binding, decreases activity, decreases reaction, increases reaction, decreases response to substance (+7 more)	10
Valproic Acid	affects cotreatment, increases expression	7
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance, increases expression (+1 more)	5
5-((2,6-dichlorobenzyl)sulfonyl)-3-((3,5-dimethyl-4-((2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-1,3-dihydro-2H-indol-2-one	increases activity, increases phosphorylation, decreases phosphorylation, increases mutagenesis, increases reaction (+4 more)	5
Quercetin	decreases expression, decreases reaction, affects binding, increases reaction, increases expression (+1 more)	4
Tretinoin	decreases reaction, increases expression, decreases expression	4
Resveratrol	affects cotreatment, decreases expression, increases expression	3
Benzo(a)pyrene	decreases methylation, increases expression, decreases expression	3
Cadmium	increases abundance, increases ubiquitination, increases activity, increases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
bisphenol A	increases expression, increases methylation	2
trichostatin A	increases expression	2
evodiamine	affects reaction, decreases reaction, increases phosphorylation, increases expression	2
((3Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-((4-methylpiperazin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide)	decreases reaction, increases phosphorylation, decreases activity	2
Erlotinib Hydrochloride	decreases phosphorylation, affects cotreatment	2
Arsenic Trioxide	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	2
Diclofenac	increases expression, decreases expression	2
Lipopolysaccharides	increases expression, increases reaction, decreases reaction	2
Methotrexate	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Plant Extracts	decreases reaction, increases phosphorylation, affects cotreatment, decreases expression	2
Aflatoxin B1	decreases methylation, decreases expression	2
Cadmium Chloride	increases ubiquitination, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine	decreases phosphorylation	1
osimertinib	decreases phosphorylation, decreases expression	1
A-1155463	affects reaction, affects response to substance, decreases reaction, increases response to substance	1
licocoumarone	decreases expression	1

ChEMBL screening assays

2015 unique, capped per target: 2005 binding, 6 functional, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003887	Binding	Inhibition of MET	Discovery of pyrrolopyridine-pyridone based inhibitors of Met kinase: synthesis, X-ray crystallographic analysis, and biological activities. — J Med Chem
CHEMBL1963775	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MET	PubChem BioAssay data set
CHEMBL4313076	ADMET	Inhibition of human c-MET using poly (Glu, Tyr)4:1 as substrate measured after 60 mins by ELISA relative to control	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

64 cell lines: 52 cancer cell line, 7 spontaneously immortalized cell line, 3 transformed cell line, 2 hybrid cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0102	SNU-638	Cancer cell line	Male
CVCL_0D41	NZM078	Cancer cell line	Sex unspecified
CVCL_1263	HCC2218	Cancer cell line	Female
CVCL_1326	Karpas-45	Cancer cell line	Male
CVCL_1714	SUP-T1	Cancer cell line	Male
CVCL_1E03	BC7	Cancer cell line	Male
CVCL_1H35	Sup-T1 Nef-ER 31	Cancer cell line	Male
CVCL_5086	SNU-719	Cancer cell line	Male
CVCL_9647	YCCEL1	Cancer cell line	Male
CVCL_9662	YCC-6	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00414765	PHASE4	COMPLETED	Aldesleukin in Participants With Metastatic Renal Cell Carcinoma or Metastatic Melanoma
NCT00777504	PHASE4	UNKNOWN	Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors
NCT00930345	PHASE4	TERMINATED	Biological, Pathological and Imagery Markers in the First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma
NCT01206764	PHASE4	COMPLETED	A Trial of Everolimis in Patients With Advanced Renal Cell Carcinoma.
NCT01266837	PHASE4	COMPLETED	Open Label, Single Arm Trial to Characterize Patients With Metastatic RCC Treated With Everolimus After Failure of the First VEGF-targeted Therapy (MARC-2)
NCT02056587	PHASE4	COMPLETED	Everolimus in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
NCT02338570	PHASE4	TERMINATED	Outcome-related Factors in Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus (ORCHIDEE)
NCT02596035	PHASE4	COMPLETED	An Investigational Immuno-therapy Safety Trial of Nivolumab in Patients With Advanced or Metastatic Renal Cell Carcinoma
NCT02982954	PHASE4	COMPLETED	A Study to Evaluate the Safety of Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Cancer
NCT05949424	PHASE4	UNKNOWN	OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
NCT07028125	PHASE4	RECRUITING	Digital Monitoring of Self-reported Symptoms by Patients Treated With Cabozantinib Plus Nivolumab for Advanced Clear-cell Renal Carcinoma
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT05043090	PHASE3	ACTIVE_NOT_RECRUITING	Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic PRCC
NCT06146777	PHASE3	NOT_YET_RECRUITING	Multi-classifier System for Stratifying Stage III Papillary Renal Cell Carcinoma of Receiving Adjuvant Therapy
NCT00033904	PHASE3	COMPLETED	Survival Study Of Oncophage® vs. Observation In Patients With Kidney Cancer
NCT00126178	PHASE3	TERMINATED	Clinical Trial Studying a Personalized Cancer Vaccine in Patients With Non-metastatic Kidney Cancer
NCT00291369	PHASE3	COMPLETED	Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis
NCT00410124	PHASE3	COMPLETED	RAD001 Plus Best Supportive Care (BSC) Versus BSC Plus Placebo in Patients With Metastatic Carcinoma of the Kidney Which Has Progressed After Treatment With Sorafenib and/or Sunitinib
NCT00474786	PHASE3	COMPLETED	Temsirolimus Versus Sorafenib As Second-Line Therapy In Patients With Advanced RCC Who Have Failed First-Line Sunitinib
NCT00478114	PHASE3	COMPLETED	Efficacy and Safety of Sorafenib in Advanced Renal Cell Carcinoma (RCC)
NCT00606632	PHASE3	COMPLETED	Pre-surgical Detection of Clear Cell Renal Cell Carcinoma (ccRCC) Using Radiolabeled G250-Antibody
NCT00606866	PHASE3	COMPLETED	MRI Study of BAY 43-9006 in Metastatic Renal Cell Carcinoma
NCT00631371	PHASE3	COMPLETED	Study Comparing Bevacizumab + Temsirolimus vs. Bevacizumab + Interferon-Alfa In Advanced Renal Cell Carcinoma Subjects
NCT00732914	PHASE3	COMPLETED	Sequential Study to Treat Renal Cell Carcinoma
NCT00869011	PHASE3	UNKNOWN	Exercise for Patients With Renal Cell Cancer Receiving Sunitinib
NCT00930033	PHASE3	COMPLETED	Clinical Trial to Assess the Importance of Nephrectomy
NCT01030783	PHASE3	COMPLETED	A Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma
NCT01076010	PHASE3	COMPLETED	An Extension Treatment Protocol for Subjects Who Have Participated in a Study of Tivozanib Versus Sorafenib in Kidney Carcinoma (Protocol AV-951-09-301).
NCT01198158	PHASE3	TERMINATED	Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy
NCT01223027	PHASE3	COMPLETED	Study of Dovitinib Versus Sorafenib in Patients With Metastatic Renal Cell Carcinoma
NCT01224288	PHASE3	ACTIVE_NOT_RECRUITING	Dynamic Contrast Enhancement Computed Tomography for Evaluating Tumor Perfusion in Patients With Metastatic Renal Cell Carcinoma Receiving Targeted Therapies: Renal Cell Carcinoma (RCC) Scramble
NCT01235962	PHASE3	COMPLETED	A Study to Evaluate Pazopanib as an Adjuvant Treatment for Localized Renal Cell Carcinoma (RCC)
NCT01265810	PHASE3	COMPLETED	Caphosol in Oral Mucositis Due to Targeted Therapy
NCT01265901	PHASE3	COMPLETED	IMA901 in Patients Receiving Sunitinib for Advanced/Metastatic Renal Cell Carcinoma
NCT01481870	PHASE3	UNKNOWN	Comparison of Sequential Therapies With Sunitinib and Sorafenib in Advanced Renal Cell Carcinoma
NCT01582672	PHASE3	TERMINATED	Phase 3 Trial of Autologous Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma
NCT01613846	PHASE3	COMPLETED	Phase III Sequential Open-label Study to Evaluate the Efficacy and Safety of Sorafenib Followed by Pazopanib Versus Pazopanib Followed by Sorafenib in the Treatment of Advanced / Metastatic Renal Cell Carcinoma (SWITCH-II)
NCT01762592	PHASE3	WITHDRAWN	REDECT 2: REnal Masses: Pivotal Trial to DEteCT Clear Cell Renal Cell Carcinoma With PET/CT
NCT01865747	PHASE3	COMPLETED	A Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma
NCT02231749	PHASE3	COMPLETED	Nivolumab Combined With Ipilimumab Versus Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 214)