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
• Clinical variants (ClinVar): 4,941 total — 5 pathogenic, 2 likely-pathogenic (top 1% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 6 regions constrained (≈1% of expected missense variation)
• GTEx eGene: eQTL in 30 tissues, sQTL in 2 (q < 0.05)
• Drug target: yes — 37 curated mechanism-of-action drugs; 95 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 6 — Amivantamab, Beperminogene Perplasmid, Cabozantinib S-Malate, +3 more
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.45 (moderately constrained)
• MANE Select transcript: NM_000245
• Interaction hub: 3,062 STRING partners (top 2% of genes corpus-wide)

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: 12 — 10 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000397752

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 3: 1, TSL 5: 2

ENST00000397752, ENST00000318493, ENST00000422097, ENST00000436117, ENST00000454623, ENST00000456159, ENST00000495962, ENST00000917365, ENST00000950406, ENST00000950407, ENST00001112056, ENST00001139670

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.

Highest expression (Bgee): pigmented layer of retina, germinal epithelium of ovary, cartilage tissue, parietal pleura, calcaneal tendon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MET is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 30 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 32 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Caudate basal ganglia	eqtl	6.9e-61	+0.91	7:116775956:G:T
Artery Aorta	eqtl	6.1e-54	-0.65	7:116777794:G:C
Brain Putamen basal ganglia	eqtl	2.8e-48	-0.89	7:116747967:C:T
Artery Tibial	eqtl	1.1e-41	-0.40	7:116777794:G:C
Brain Nucleus accumbens basal ganglia	eqtl	6.7e-32	-0.67	7:116806828:C:A
Brain Spinal cord cervical c-1	eqtl	1.9e-31	+0.83	7:116765333:T:C
Brain Substantia nigra	eqtl	9.9e-22	-0.81	7:116739040:C:T
Brain Hypothalamus	eqtl	4.3e-17	+0.57	7:116781913:T:C
Brain Amygdala	eqtl	4.0e-16	-0.73	7:116739040:C:T
Colon Sigmoid	eqtl	3.7e-12	-0.36	7:116777794:G:C
Esophagus Muscularis	eqtl	9.9e-12	-0.30	7:116777794:G:C
Brain Cerebellar Hemisphere	eqtl	7.6e-10	-0.47	7:116805037:G:A
Brain Cerebellum	eqtl	1.4e-09	-0.46	7:116795968:G:A
Brain Hippocampus	eqtl	2.7e-07	-0.29	7:116806828:C:A
Thyroid	eqtl	5.8e-07	+0.17	7:116730233:G:T
Lung	eqtl	7.4e-07	-0.15	7:116765333:T:C
Nerve Tibial	eqtl	1.4e-04	-0.14	7:116717990:A:G
Cells EBV-transformed lymphocytes	eqtl	1.6e-04	-0.73	7:116633835:ACT:A
Brain Cortex	eqtl	4.5e-04	-0.23	7:116807554:C:T
Breast Mammary Tissue	eqtl	5.8e-04	+0.15	7:116807722:C:T

FANTOM5 promoters

showing 10 of 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

showing 100 of 290 tissues 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
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.01	gold quality
liver	UBERON:0002107	90.64	gold quality
pericardium	UBERON:0002407	90.10	gold quality
gingiva	UBERON:0001828	90.06	gold quality
jejunal mucosa	UBERON:0000399	89.99	gold quality
synovial joint	UBERON:0002217	89.71	gold quality
vastus lateralis	UBERON:0001379	89.63	gold quality
islet of Langerhans	UBERON:0000006	89.18	gold quality
choroid plexus epithelium	UBERON:0003911	89.11	gold quality
renal glomerulus	UBERON:0000074	89.10	gold quality
metanephric glomerulus	UBERON:0004736	88.76	gold quality
triceps brachii	UBERON:0001509	88.74	gold quality
epithelium of nasopharynx	UBERON:0001951	88.60	gold quality
endometrium	UBERON:0001295	88.14	gold quality
quadriceps femoris	UBERON:0001377	88.09	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.07	gold quality
endothelial cell	CL:0000115	87.98	silver quality
deltoid	UBERON:0001476	87.96	gold quality
nasal cavity mucosa	UBERON:0001826	87.96	gold quality
trigeminal ganglion	UBERON:0001675	87.70	gold quality
skeletal muscle tissue	UBERON:0001134	87.59	gold quality
renal medulla	UBERON:0000362	87.58	gold quality
mammary duct	UBERON:0001765	87.55	gold quality
epithelium of mammary gland	UBERON:0003244	87.47	gold quality
kidney	UBERON:0002113	86.96	gold quality
mammary gland	UBERON:0001911	86.91	gold quality
thoracic mammary gland	UBERON:0005200	86.88	gold quality
cervix squamous epithelium	UBERON:0006922	86.66	silver quality
jejunum	UBERON:0002115	86.26	gold quality
diaphragm	UBERON:0001103	86.14	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.07	gold quality
squamous epithelium	UBERON:0006914	85.99	gold quality
cortex of kidney	UBERON:0001225	85.77	gold quality
primary visual cortex	UBERON:0002436	85.74	gold quality
layer of synovial tissue	UBERON:0007616	85.69	gold quality
right lobe of liver	UBERON:0001114	85.67	gold quality
muscle tissue	UBERON:0002385	85.53	gold quality
occipital lobe	UBERON:0002021	85.01	gold quality
CA1 field of hippocampus	UBERON:0003881	84.63	gold quality
parotid gland	UBERON:0001831	84.49	gold quality
upper leg skin	UBERON:0004262	84.46	gold quality
adult mammalian kidney	UBERON:0000082	84.36	gold quality
metanephros	UBERON:0000081	84.28	gold quality
muscle organ	UBERON:0001630	84.24	gold quality
duodenum	UBERON:0002114	84.11	gold quality
urinary bladder	UBERON:0001255	84.05	gold quality
lung	UBERON:0002048	83.95	gold quality
heart right ventricle	UBERON:0002080	83.91	gold quality
gall bladder	UBERON:0002110	83.59	gold quality
sural nerve	UBERON:0015488	83.44	gold quality
esophagus squamous epithelium	UBERON:0006920	83.27	gold quality
urethra	UBERON:0000057	83.03	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.01	gold quality
tendon of biceps brachii	UBERON:0008188	82.64	gold quality
oral cavity	UBERON:0000167	82.63	gold quality
muscle of leg	UBERON:0001383	82.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.27	gold quality
dorsal root ganglion	UBERON:0000044	82.12	gold quality
cervix epithelium	UBERON:0004801	81.94	silver quality
gastrocnemius	UBERON:0001388	81.81	gold quality
tibialis anterior	UBERON:0001385	81.67	gold quality
oviduct epithelium	UBERON:0004804	81.55	gold quality
mammalian vulva	UBERON:0000997	81.40	gold quality
pancreas	UBERON:0001264	81.30	gold quality
colonic epithelium	UBERON:0000397	81.27	gold quality
rectum	UBERON:0001052	81.07	gold quality
connective tissue	UBERON:0002384	81.06	gold quality
epithelium of esophagus	UBERON:0001976	80.90	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.88	gold quality
adipose tissue	UBERON:0001013	80.82	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 159 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebellum	tissue	60.4	high
Bone marrow	tissue	54.5	high
Thymus	tissue	53.4
Retina	tissue	41.6
Tonsil	tissue	41.3	high
Tongue	tissue	40.8
Liver	tissue	40.1	medium
Lymph node	tissue	39.9	high
Skeletal muscle	tissue	37.6	high
Stomach 1	tissue	36.7	high
Corpus callosum	tissue	36.0
Olfactory bulb	tissue	36.0
Putamen	tissue	34.1
Parathyroid gland	tissue	33.9	high
Skin 1	tissue	33.0	high
Liver	tissue	32.7	medium
Spleen	tissue	32.5	medium
Thyroid gland	tissue	31.7	high
Periaqueductal gray	tissue	31.7
Urinary bladder	tissue	31.6	high
Septum	tissue	31.5
Cerebral cortex	tissue	31.4	high
Somatosensory cortex	tissue	31.4
Occipital cortex	tissue	31.2
Amygdala	tissue	31.1
Retrosplenial cortex	tissue	30.2
Rectum	tissue	30.1	high
Hippocampal formation	tissue	30.0
Entorhinal cortex	tissue	30.0
Vagina	tissue	29.9	high
Spinal cord	tissue	29.7
Appendix	tissue	29.7	medium
Prefrontal cortex	tissue	29.6
Adipose tissue	tissue	29.3	high
Substantia nigra	tissue	29.0
Motor cortex	tissue	28.9
Retrosplenial and cingulate cortex	tissue	28.9
Thalamus	tissue	28.7
Kidney	tissue	28.7	high
Ventral forebrain	tissue	28.6
Medulla oblongata	tissue	28.5
Superior colliculi	tissue	28.5
Temporal cortex	tissue	28.3
Basal ganglia	tissue	28.2	high
Hypothalamus	tissue	28.2
Duodenum	tissue	28.2	high
Midbrain	tissue	27.9
Insular cortex	tissue	27.8
Pons	tissue	27.1
Small intestine	tissue	27.1	high
Colon	tissue	27.0	high
Breast	tissue	26.8	high
Pituitary gland	tissue	26.7
Esophagus	tissue	26.7	high
Lung	tissue	26.6	high
Salivary gland	tissue	26.4	high
Testis	tissue	26.0	high
Choroid plexus	tissue	25.6
Choroid plexus	tissue	25.1
Placenta	tissue	24.8	medium

Brain sub-regions (HPA Brain Atlas): detected in 384; highest nTPM — Cerebellar cortex (44.3), Flocculonodular lobe (40.5), Vermis (37.8), White matter (36.0), Area striata (white matter) (34.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting MET by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 160 miRNAs:

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

gnomAD constraint: pLI 1, LOEUF 0.446, missense Z 2.97 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000397752 splits into 6 regions with different missense tolerance; 1 is missense-constrained (≈1% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
7:116,699,085–116,757,486	762 / 792.4	0.96	no
7:116,757,487–116,782,039	514 / 659.6	0.78	no
7:116,782,040–116,782,095	2 / 21.5	0.09	yes (p 2.6e-05)
7:116,782,096–116,783,401	38 / 40.6	0.94	no
7:116,783,402–116,795,774	32 / 72.4	0.44	no
7:116,795,775–116,796,121	94 / 109.5	0.86	no

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), RET (ENSG00000165731), AXL (ENSG00000167601), ROR2 (ENSG00000169071), ALK (ENSG00000171094), INSR (ENSG00000171105), ERBB4 (ENSG00000178568), CSF1R (ENSG00000182578), EPHB3 (ENSG00000182580), EPHA10 (ENSG00000183317), ROR1 (ENSG00000185483), EPHB4 (ENSG00000196411), NTRK1 (ENSG00000198400), DDR1 (ENSG00000204580)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96969) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 72 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal liver development	2
abnormal myogenesis	2
increased sarcoma incidence	2
abnormal diaphragm morphology	2
abnormal muscle precursor cell migration	2
hypaxial muscle hypoplasia	2
decreased liver weight	2
impaired liver regeneration	2
lethality throughout fetal growth and development, complete penetrance	2
hydronephrosis	1
small liver	1
dilated liver sinusoidal space	1
thin diaphragm muscle	1
abnormal tongue morphology	1
abnormal cerebral cortex morphology	1
abnormal primary somatosensory cortex morphology	1
abnormal motor neuron innervation pattern	1
abnormal somatic motor system morphology	1
abnormal lung development	1
overexpanded pulmonary alveolus	1
abnormal placenta development	1
decreased trophoblast giant cell number	1
abnormal placenta labyrinth morphology	1
impaired wound healing	1
increased mammary adenocarcinoma incidence	1

+47 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Felis catus	A0M8S8	100.0%	Diamond
Neofelis nebulosa	Q07E37	100.0%	Diamond
Pan troglodytes	Q2QLF1	99.8%	Diamond
Gorilla gorilla gorilla	Q2IBF2	99.7%	Diamond
Pongo abelii	Q2IBD8	99.5%	Diamond
Papio anubis	A0M8R7	99.3%	Diamond
Colobus guereza	Q07DZ1	99.3%	Diamond
Chlorocebus aethiops	Q2IBA6	99.3%	Diamond
Aotus nancymaae	Q07DV8	99.1%	Diamond
Nomascus leucogenys	Q07DY1	99.1%	Diamond
Ateles geoffroyi	Q09YL1	99.1%	Diamond
Drosophila sechellia	B4HNW4	99.0%	Diamond
Drosophila simulans	B4QC63	99.0%	Diamond
Saimiri boliviensis boliviensis	Q09YH7	99.0%	Diamond
Drosophila persimilis	B4GBH0	98.9%	Diamond
Drosophila pseudoobscura pseudoobscura	Q290N5	98.9%	Diamond
Plecturocebus moloch	Q2QLC0	98.6%	Diamond
Drosophila melanogaster	Q6AWJ9	98.5%	Diamond
Callithrix jacchus	Q2QLG5	97.7%	Diamond
Ovis aries	Q09YI9	97.5%	Diamond
Bos taurus	Q769I5	97.5%	Diamond
Drosophila erecta	B3NS99	97.4%	Diamond
Drosophila yakuba	B4P5Q9	97.4%	Diamond
Muntiacus muntjak	Q09YK0	97.4%	Diamond
Eulemur macaco macaco	Q2IBG7	97.4%	Diamond
Microcebus murinus	Q2QL89	97.4%	Diamond
Mustela putorius furo	Q07E24	96.4%	Diamond
Canis lupus familiaris	Q75ZY9	96.4%	Diamond
Xenopus tropicalis	A0JM20	95.5%	Diamond
Xenopus laevis	Q8QFP9	95.5%	Diamond
Equus caballus	Q2QLA9	94.9%	Diamond
Sus scrofa	Q2QLE0	94.9%	Diamond
Otolemur garnettii	Q2QLH6	94.0%	Diamond
Gallus gallus	Q9DF58	92.9%	Diamond
Atelerix albiventris	Q00PJ8	92.0%	Diamond
Loxodonta africana	Q108U6	91.8%	Diamond
Dasypus novemcinctus	Q07E48	91.4%	Diamond
Oryctolagus cuniculus	Q09YN5	91.2%	Diamond
Rhinolophus ferrumequinum	Q2IBC0	90.1%	Diamond
Drosophila ananassae	B3MH43	88.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CAPZA2	protein-coding	830
CAV1	protein-coding	857
CAV2	protein-coding	858
COMETT	ncRNA	100996266
CAV2-DT	ncRNA	107986838
ST7-OT4	ncRNA	338069
ST7	protein-coding	7982
ST7-AS1	ncRNA	93653

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): C9JKM5, P08581, 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)

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

UniProt features (234 total): strand 75, helix 42, sequence variant 37, 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)

showing 30 of 130 structures by resolution:

PDB	Title	Method	Resolution (Å)
9T6K	Crystal structure of wild-type c-MET bound by glumetinib.	X-RAY DIFFRACTION	1.13
9T0D	Crystal structure of wild-type c-MET bound by glesatinib	X-RAY DIFFRACTION	1.2
4R1V	Identification and optimization of pyridazinones as potent and selective c-Met kinase …	X-RAY DIFFRACTION	1.2
9SXJ	Crystal structure of wild-type c-MET bound by capmatinib.	X-RAY DIFFRACTION	1.31
3BUX	Crystal structure of c-Cbl-TKB domain complexed with its binding motif in c-Met	X-RAY DIFFRACTION	1.35
3F66	Human c-Met Kinase in complex with quinoxaline inhibitor	X-RAY DIFFRACTION	1.4
3ZCL	X-ray Structure of c-Met kinase in complex with inhibitor …	X-RAY DIFFRACTION	1.4
9T08	Crystal structure of wild-type c-MET bound by sitravatinib.	X-RAY DIFFRACTION	1.46
3DKC	Structure of MET receptor tyrosine kinase in complex with ATP	X-RAY DIFFRACTION	1.52
9T0B	Crystal structure of D1228V c-MET bound by sitravatinib.	X-RAY DIFFRACTION	1.54
9C1R	Crystal structure of mutant cMET D1228N kinase domain in complex with inhibitor compound …	X-RAY DIFFRACTION	1.59
3Q6U	Structure of the apo MET receptor kinase in the dually-phosphorylated, activated state	X-RAY DIFFRACTION	1.6
9T3Q	Crystal structure of D1228V c-MET bound by cabozantinib.	X-RAY DIFFRACTION	1.63
4MXC	Crystal structure of CMET in complex with novel inhibitor	X-RAY DIFFRACTION	1.63
5HTI	Crystal structure of c-Met kinase domain in complex with LXM108	X-RAY DIFFRACTION	1.66
9T2V	Crystal structure of wild-type c-MET bound by cabozantinib.	X-RAY DIFFRACTION	1.67
6SDC	Crystal structure of D1228V cMET bound by foretinib	X-RAY DIFFRACTION	1.67
7V3R	Crystal structure of CMET in complex with a novel inhibitor	X-RAY DIFFRACTION	1.7
5HNI	CRYSTAL STRUCTURE OF CMET WT with compound 3	X-RAY DIFFRACTION	1.71
3Q6W	Structure of dually-phosphorylated MET receptor kinase in complex with an MK-2461 analog …	X-RAY DIFFRACTION	1.75
4XMO	Crystal structure of c-Met in complex with …	X-RAY DIFFRACTION	1.75
5EOB	Crystal structure of CMET in complex with novel inhibitor	X-RAY DIFFRACTION	1.75
7B3Q	Crystal structure of c-MET bound by compound 1	X-RAY DIFFRACTION	1.75
7B40	Crystal structure of c-MET bound by compound 6	X-RAY DIFFRACTION	1.76
7B44	Crystal structure of c-MET bound by compound S1	X-RAY DIFFRACTION	1.76
8OUU	Crystal structure of D1228V c-MET bound by compound 29	X-RAY DIFFRACTION	1.77
8OUV	Crystal structure of D1228V c-MET bound by compound 15	X-RAY DIFFRACTION	1.78
1R0P	Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor …	X-RAY DIFFRACTION	1.8
1R1W	CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF THE HEPATOCYTE GROWTH FACTOR RECEPTOR …	X-RAY DIFFRACTION	1.8
3DKF	Structure of MET receptor tyrosine kinase in complex with inhibitor SGX-523	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

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

Antibody-complex structures (SAbDab)

6 antibodies co-crystallized with this protein: 4K3J, 5LSP, 6I04, 6WVZ, AMIVANTAMAB, ONARTUZUMAB

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, Transporters, Accessory Factors Involved in Transport, Predicted membrane proteins, Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, RAS pathway related proteins, Cancer-related genes, Candidate cancer biomarkers, Mutated cancer genes, Disease related genes, FDA approved drug targets, Biotech drugs, Small molecule drugs, Human disease related genes, Ear disease

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; cytosol

Antibody reliability (HPA): IH approved · IF approved

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)

Position	Role
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)

Position	Role
1084–1092	ATP
1110	ATP

Post-translational modifications (13)

Type	Positions
Phosphoserine	966, 990, 997, 1000
Phosphothreonine	977, 1289
Phosphotyrosine	1003, 1230, 1234, 1235, 1349, 1356, 1365

Disulfide bonds (12)

Type	Positions
Disulfide bond	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)

Type	Positions
N-linked (glcnac…) asparagine	45, 106, 149, 202, 399, 405, 607, 635, 785, 879, 930
O-linked (man) threonine	582, 676, 761

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 interaction with …
1235	complete loss of kinase activity. alters interaction with ptpn1 and ptpn2. loss of interaction with ptpn1 and ptpn2; when associated with …
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

18 curated (TAS) of 44; 8 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

44 pathways:

ID	Pathway	Evidence
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer ⚕	curated
R-HSA-9734091	Drug-mediated inhibition of MET activation	curated
R-HSA-9022699	MECP2 regulates neuronal receptors and channels	curated
R-HSA-6806942	MET Receptor Activation	curated
R-HSA-8851907	MET activates PI3K/AKT signaling	curated
R-HSA-8874081	MET activates PTK2 signaling	curated
R-HSA-8865999	MET activates PTPN11	curated
R-HSA-8875555	MET activates RAP1 and RAC1	curated
R-HSA-8851805	MET activates RAS signaling	curated
R-HSA-8875791	MET activates STAT3	curated
R-HSA-8875513	MET interacts with TNS proteins	curated
R-HSA-8875656	MET receptor recycling	curated
R-HSA-6807004	Negative regulation of MET activity	curated
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	curated
R-HSA-1257604	PIP3 activates AKT signaling	curated
R-HSA-5673001	RAF/MAP kinase cascade	curated
R-HSA-9825892	Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	curated
R-HSA-416550	Sema4D mediated inhibition of cell attachment and migration	curated
R-HSA-9824439	Bacterial Infection Pathways ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-8875360	InlB-mediated entry of Listeria monocytogenes into host cell ⚕	electronic
R-HSA-8876384	Listeria monocytogenes entry into host cells ⚕	—
R-HSA-2219528	PI3K/AKT Signaling in Cancer ⚕	—
R-HSA-422475	Axon guidance	—
R-HSA-1266738	Developmental Biology	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-5683057	MAPK family signaling cascades	—
R-HSA-5684996	MAPK1/MAPK3 signaling	—
R-HSA-8875878	MET promotes cell motility	—
R-HSA-9856651	MITF-M-dependent gene expression	—
R-HSA-9730414	MITF-M-regulated melanocyte development	—
R-HSA-199418	Negative regulation of the PI3K/AKT network	—
R-HSA-9675108	Nervous system development	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-400685	Sema4D in semaphorin signaling	—
R-HSA-373755	Semaphorin interactions	—
R-HSA-162582	Signal Transduction	—
R-HSA-6806834	Signaling by MET	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—
R-HSA-8986944	Transcriptional Regulation by MECP2	—

MSigDB gene sets: 0 (showing top):

GO Biological Process (19): 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), regulation of gene expression (GO:0010468), cell development (GO:0048468), animal organ development (GO:0048513)

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

11 top-level categories:

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

showing 60 of 66 GO namespaces:

Category	Terms
cellular anatomical structure	4
cell differentiation	2
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
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
gene expression	1
regulation of macromolecule biosynthetic process	1
anatomical structure development	1
cellular developmental process	1
animal gross anatomical part developmental process	1
protein kinase activity	1
transmembrane receptor protein tyrosine kinase activity	1
hepatocyte growth factor binding	1
hepatocyte growth factor receptor signaling pathway	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
transmembrane signaling receptor activity	1
semaphorin-plexin signaling pathway	1
phosphatase binding	1
protein binding	1
molecular function regulator activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein tyrosine kinase activity	1
transmembrane receptor protein kinase activity	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 39 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO term	NS	Evidence
branching morphogenesis of an epithelial tube	BP	mutant phenotype
endothelial cell morphogenesis	BP	direct assay
hepatocyte growth factor receptor signaling pathway	BP	direct assay
negative regulation of hydrogen peroxide-mediated programmed cell death	BP	mutant phenotype
positive chemotaxis	BP	direct assay
positive regulation of endothelial cell chemotaxis	BP	mutant phenotype
positive regulation of transcription by RNA polymerase II	BP	direct assay
semaphorin-plexin signaling pathway	BP	direct assay
basal plasma membrane	CC	direct assay
cell surface	CC	high-throughput assay
identical protein binding	MF	physical interaction
molecular function activator activity	MF	experiment
protein phosphatase binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 3,062 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MET	HGF	P14210	941
MET	MACC1	Q6ZN28	802
MET	EGF	P01133	767
MET	PIK3CA	P42336	751
MET	PIK3CG	P48736	720
MET	PIK3CD	O00329	719
MET	PIK3CB	P42338	719
MET	SH3KBP1	Q96B97	719
MET	GRB2	P29354	706
MET	MTOR	P42345	706
MET	KRAS	P01116	679
MET	CTNNB1	P35222	679
MET	TP53	P04637	677
MET	STAT3	P40763	666
MET	CDH1	P12830	657

IntAct

Human interaction partners of MET in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 99 partners by confidence:

Partner	Interaction type	MIscore	Records
CBL	proximity	0.860	17
HGF	direct interaction	0.850	11
EGFR	phosphorylation reaction	0.800	7
SRC	association	0.790	6
PLXNB1	physical association	0.780	9
PTPRJ	physical association	0.730	5
PTPN1	physical association	0.710	3
DNAJA3	physical association	0.640	4
PTPN11	physical association	0.610	13
PTK2	phosphorylation reaction	0.600	5
RANBP9	direct interaction	0.590	3
MNDA	physical association	0.560	3
PLXNB2	physical association	0.520	2
PLXNB3	physical association	0.520	2
PREX1	physical association	0.520	2
NTRK3	physical association	0.500	1
LAPTM4B	colocalization	0.460	3
RASA1	direct interaction	0.440	15
PIK3R2	direct interaction	0.440	11
PIK3R3	direct interaction	0.440	11
PLCG1	direct interaction	0.440	10
SH2D2A	direct interaction	0.440	7
PIK3R1	direct interaction	0.440	6
SH2D1B	direct interaction	0.440	6
SHC1	direct interaction	0.440	5
SH2D3C	direct interaction	0.440	4
SHB	direct interaction	0.440	4
SLA2	direct interaction	0.440	4
SOCS6	direct interaction	0.440	4
LCK	direct interaction	0.440	3

BioGRID (583 interactions; top human partners by supporting records): CBL (Far Western; 18 records), GLMN (Two-hybrid; 6 records), HGF (Protein-peptide; 6 records), EGFR (Affinity Capture-MS; 5 records), CANX (Affinity Capture-Western; 4 records), ERBB2 (PCA; 4 records), GRB2 (Reconstituted Complex; 4 records), HSPA5 (Affinity Capture-Western; 4 records), SOCS1 (Affinity Capture-Western; 4 records), CEACAM21 (Affinity Capture-MS; 3 records), DNAJB11 (Affinity Capture-Western; 3 records), GAB1 (Affinity Capture-Western; 3 records), GSK3B (Affinity Capture-MS; 3 records), HSP90AA1 (Affinity Capture-Western; 3 records), HSPA1B (Affinity Capture-MS; 3 records)

SIGNOR signaling

showing 41 of 81 signaling 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”
PHA-665752	down-regulates	MET	“chemical inhibition”
SGX-523	down-regulates	MET	“chemical inhibition”
SU11274	down-regulates	MET	“chemical inhibition”
cabozantinib	down-regulates	MET	“chemical inhibition”
PTPN2	“down-regulates activity”	MET	dephosphorylation
PTPN1	“down-regulates activity”	MET	dephosphorylation
PTPRB	“down-regulates activity”	MET	dephosphorylation
PTPRJ	“down-regulates activity”	MET	dephosphorylation
MET	“up-regulates activity”	GAB1	phosphorylation
PAX7-FOXO1	“up-regulates quantity by expression”	MET	“transcriptional regulation”
PAX3-FOXO1	“up-regulates quantity by expression”	MET	“transcriptional regulation”
NME1	“down-regulates quantity by repression”	MET	“transcriptional regulation”
MET	“up-regulates activity”	GRB2	binding
MET	up-regulates	Metastasis
MECP2	“down-regulates quantity by repression”	MET	“post transcriptional regulation”
MACC1	“up-regulates quantity by expression”	MET	“transcriptional regulation”
USP8	“down-regulates quantity”	MET	destabilization
FOXP2	“down-regulates quantity by repression”	MET	“transcriptional regulation”
HOTAIR	down-regulates	MET
MET	“up-regulates activity”	GSK3B	phosphorylation
MET	“up-regulates activity”	IQGAP1	phosphorylation
MET	“up-regulates activity”	CAV1	phosphorylation
MET	“up-regulates activity”	PARP1	phosphorylation

Protein complexes (CORUM) (18)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

showing 17 of 18 complexes by size:

Complex	Subunits	Members
★ ITGA6-ITGB4-MET-PIK3R1-SHC1 complex	5	PIK3R1, SHC1, ITGA6, ITGB4, MET
★ CBL-MET-SH3GL3-SH3KBP1 complex	4	CBL, MET, SH3GL3, SH3KBP1
★ AXL-DOCK1-ELMO2-MET complex	4	AXL, DOCK1, ELMO2, MET
★ CD151-ITGB4-MET complex	3	ITGB4, MET, CD151
★ ITGAV-ITGB1-MET complex	3	ITGAV, ITGB1, MET
★ ITGB4-MET-S1PR1 complex	3	ITGB4, MET, S1PR1
★ FER-MET complex	2	FER, MET
★ EGFR-MET complex	2	EGFR, MET
★ CD82-MET complex	2	CD82, MET
★ MET-PLXNB1 complex	2	MET, PLXNB1
★ MET-NRP1 complex	2	NRP1, MET
★ ERBB3-MET complex	2	ERBB3, MET
★ ERBB2-MET complex	2	ERBB2, MET
★ MET-RET complex	2	MET, RET
★ MET-MST1R complex	2	MET, MST1R
★ KDR-MET complex	2	KDR, MET
★ HGF-MET complex	2	HGF, MET

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 99 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of KIT signaling	11	78.7×	1e-17
Constitutive Signaling by EGFRvIII	9	76.5×	2e-14
Tie2 Signaling	9	64.4×	1e-13
Signaling by ERBB2 ECD mutants	8	64.0×	4e-12
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	10	61.8×	8e-15
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	9	61.2×	2e-13
Negative regulation of FLT3	7	59.5×	2e-10
Signaling by SCF-KIT	20	59.1×	5e-29

GO biological processes:

GO term	Partners	Fold	FDR
Fc-gamma receptor signaling pathway involved in phagocytosis	9	65.2×	9e-13
Fc-epsilon receptor signaling pathway	8	60.4×	5e-11
B cell receptor signaling pathway	14	57.9×	9e-19
peptidyl-tyrosine phosphorylation	11	47.8×	7e-14
peptidyl-tyrosine dephosphorylation	5	45.7×	3e-06
negative regulation of receptor signaling pathway via JAK-STAT	5	45.7×	3e-06
negative regulation of inflammatory response to antigenic stimulus	7	43.4×	1e-08
negative regulation of epidermal growth factor receptor signaling pathway	5	39.5×	5e-06

Disease & clinical

Genetic variants

Variant evidence for MET: 4,941 ClinVar records (7 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

4,941 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	2
Uncertain significance	2578
Likely benign	1230
Benign	127

Top pathogenic / likely-pathogenic (7)

Showing all 7 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
183686	NM_000245.4(MET):c.2521T>G (p.Phe841Val)	Pathogenic	criteria provided, single submitter	2
376126	NM_000245.4(MET):c.3749T>C (p.Met1250Thr)	Likely pathogenic	criteria provided, single submitter	2
3384110	NM_000245.4(MET):c.3503T>G (p.Phe1168Cys)	Likely pathogenic	criteria provided, single submitter	1
13882	NM_000245.4(MET):c.3562G>T (p.Val1188Leu)	Pathogenic	no assertion criteria provided	1
13889	NM_000245.4(MET):c.3750G>A (p.Met1250Ile)	Pathogenic	no assertion criteria provided	1
13890	NM_000245.4(MET):c.3731A>G (p.Lys1244Arg)	Pathogenic	no assertion criteria provided	1
998144	NM_000245.4(MET):c.2855del (p.Phe952fs)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore MET’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

AlphaMissense

2,822 missense substitutions predicted likely pathogenic (of 9,195 scored), across 692 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M1131	9	0.991	1.000
M1211	9	0.991	1.000
M1160	9	0.984	0.999
M1192	9	0.982	0.999
M1250	9	0.971	0.999
M1316	9	0.878	0.998
D1204	8	1.000	1.000
N1209	8	1.000	1.000
D1222	8	1.000	1.000
H1202	8	0.999	1.000
D1265	8	0.999	1.000
D1164	8	0.997	0.999
F1223	8	0.997	1.000
F1089	8	0.996	1.000
F1124	8	0.995	1.000
F1200	8	0.985	1.000
H1088	8	0.984	0.998
F1134	8	0.980	0.998
D1213	8	0.977	0.999
F1184	8	0.973	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (TCGA)	unfavorable	6.8e-06
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.69e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	4.09e-05
Head and Neck Squamous Cell Carcinoma (TCGA)	unfavorable	0.000297

Disease associations

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

GenCC curated gene-disease

6 curated gene-disease records:

Disease	Classification	Inheritance	Records
hereditary papillary renal cell carcinoma	Definitive	Autosomal dominant	3
papillary renal cell carcinoma	Definitive	Autosomal dominant	4
autosomal recessive nonsyndromic hearing loss 97	Strong	Autosomal recessive	2
osteofibrous dysplasia	Supportive	Autosomal dominant	2
hearing loss, autosomal recessive	Supportive	Autosomal recessive
arthrogryposis, distal, IIa 11	Limited	Autosomal dominant	2

ClinGen Gene-Disease Validity

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

3 validity classifications:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 5 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
Adult solid tumours cancer susceptibility	green
Adult solid tumours for rare disease	green
Arthrogryposis	green
Inherited renal cancer	green
Renal cancer pertinent cancer susceptibility	green
Monogenic hearing loss	amber
Paediatric disorders	amber

Mondo (12): hereditary papillary renal cell carcinoma (MONDO:0003789), renal cell carcinoma (MONDO:0005086), hereditary neoplastic syndrome (MONDO:0015356), hepatocellular carcinoma (MONDO:0007256), osteofibrous dysplasia (MONDO:0011806), autosomal recessive nonsyndromic hearing loss 97 (MONDO:0014739), arthrogryposis, distal, IIa 11 (MONDO:0031045), pediatric hepatocellular carcinoma (MONDO:0018055), arthrogryposis, distal, type 1A (MONDO:0007157), colorectal cancer (MONDO:0005575), papillary renal cell carcinoma (MONDO:0017884), hearing loss, autosomal recessive (MONDO:0019588)

Orphanet (9): Inherited cancer-predisposing syndrome (Orphanet:140162), Renal cell carcinoma (Orphanet:217071), Hereditary papillary renal cell carcinoma (Orphanet:47044), Osteofibrous dysplasia (Orphanet:488265), Hepatocellular carcinoma (Orphanet:88673), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Pediatric hepatocellular carcinoma (Orphanet:33402), Distal arthrogryposis type 1 (Orphanet:1146), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

MeSH disease descriptors

6 disease descriptors:

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
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C564609	Deafness, Autosomal Recessive *(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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the MET protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

37 curated-mechanism drugs:

Drug	Modality	Max phase
AMIVANTAMAB	Antibody	4
BEPERMINOGENE PERPLASMID	Gene	4
CABOZANTINIB S-MALATE	Small molecule	4
CAPMATINIB	Small molecule	4
CRIZOTINIB	Small molecule	4
TEPOTINIB	Small molecule	4
ONARTUZUMAB	Antibody	3
SAVOLITINIB	Small molecule	3
TELISOTUZUMAB VEDOTIN	Antibody drug conjugate	3
TEREVALEFIM	Small molecule	3
TIVANTINIB	Small molecule	3
ALTIRATINIB	Small molecule	2
AMG-208	Small molecule	2
AMG-337	Small molecule	2
AMUVATINIB	Small molecule	2
BAFISONTAMAB	Antibody	2
BMS-777607	Small molecule	2
EMIBETUZUMAB	Antibody	2
FORETINIB	Small molecule	2
GLESATINIB	Small molecule	2
GOLVATINIB	Small molecule	2
MERESTINIB	Small molecule	2
MK-2461	Small molecule	2
NINGETINIB	Small molecule	2
SAR-125844	Small molecule	2
TELISOTUZUMAB	Antibody	2
ARRY-300	Unknown	1
BMS-698769	Unknown	1
BMS-794833	Small molecule	1
BMS-817378	Unknown	1
BPI-9016	Unknown	1
EMD-1204831	Small molecule	1
JNJ-38877605	Small molecule	1
MK-8033	Small molecule	1
PF-04217903	Small molecule	1
SGX-523	Small molecule	1
TAS-115	Small molecule	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 359,247 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 95 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL2103868	CABOZANTINIB S-MALATE	4	3,378
CHEMBL3188267	CAPMATINIB	4	3,032
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL3402762	TEPOTINIB	4	1,359
CHEMBL1173655	AFATINIB	4	15,878
CHEMBL2105712	AFATINIB DIMALEATE	4	3,441
CHEMBL1289926	AXITINIB	4	16,510
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL3545311	BRIGATINIB	4	5,988
CHEMBL2105717	CABOZANTINIB	4	11,799
CHEMBL2403108	CERITINIB	4	9,002
CHEMBL2028663	DABRAFENIB	4	13,060
CHEMBL4113131	ENSARTINIB	4	737
CHEMBL1983268	ENTRECTINIB	4	3,737
CHEMBL553	ERLOTINIB	4	109,860
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL939	GEFITINIB	4	119,425
CHEMBL1852688	INFIGRATINIB	4	2,298
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	330
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL180022	NERATINIB	4
CHEMBL502835	NINTEDANIB	4
CHEMBL189963	PALBOCICLIB	4
CHEMBL477772	PAZOPANIB	4
CHEMBL1336	SORAFENIB	4
CHEMBL535	SUNITINIB	4
CHEMBL1289494	TIVOZANIB	4
CHEMBL24828	VANDETANIB	4
CHEMBL3334567	SAVOLITINIB	3
CHEMBL2103882	TIVANTINIB	3
CHEMBL31965	CANERTINIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL1879463	DACTOLISIB	3
CHEMBL300138	ENZASTAURIN	3
CHEMBL297453	EPIGALOCATECHIN GALLATE	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL1091644	LINSITINIB	3
CHEMBL3545154	POZIOTINIB	3
CHEMBL50	QUERCETIN	3
CHEMBL1241855	RIGOSERTIB	3
CHEMBL3989926	SITRAVATINIB	3
CHEMBL3545365	ALTIRATINIB	2
CHEMBL496102	AMG-208	2
CHEMBL3785909	AMG-337	2
CHEMBL460702	BMS-777607	2
CHEMBL1230609	FORETINIB	2
CHEMBL3989914	GLESATINIB	2
CHEMBL3039525	GOLVATINIB	2
CHEMBL3545307	MERESTINIB	2
CHEMBL1822792	MK-2461	2
CHEMBL3984441	NINGETINIB	2
CHEMBL4461070	SAR-125844	2
CHEMBL495727	AT-9283	2
CHEMBL3809489	BEMCENTINIB	2
CHEMBL513909	BI-2536	2
CHEMBL575448	BMS-754807	2
CHEMBL1967878	CENISERTIB	2
CHEMBL2029988	CEP-32496	2
CHEMBL3818247	DALMELITINIB	2

PharmGKB: 1 entry (CPIC guideline: no)

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 (45 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
JNJ-38877605-d1	Inhibition	8.59	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

Binding affinities (BindingDB)

4514 measured of 6088 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
US20240294535, Compound 15	IC50	0.001 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 18	IC50	0.001 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 21	IC50	0.001 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 1	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 2	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 3	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 5	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 6	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 7	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 8	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 9	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 10	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 12	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 13	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 16	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 17	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 19	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 20	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 22	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 23	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 24	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 25	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 26	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 27	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 28	IC50	0.002 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 4	IC50	0.003 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 11	IC50	0.003 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
US20240294535, Compound 14	IC50	0.003 nM	US-20240294535: IMIDAZOTRIAZINE THIOBENZAMIDE DERIVATIVE, AND PREPARATION METHOD AND APPLICATION THEREOF
CHEMBL5184459	IC50	0.019 nM
CHEMBL5174958	IC50	0.035 nM
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
CHEMBL3797911	IC50	0.12 nM
CHEMBL3582305	IC50	0.13 nM
Capmatinib	IC50	0.13 nM
(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	IC50	0.14 nM	US-20240132517: MACROCYCLIC COMPOUND, PHARMACEUTICAL COMPOSITION, AND USE THEREOF
CHEMBL6133512	IC50	0.19 nM
(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
CHEMBL1802904	IC50	0.2 nM
CHEMBL6188807	IC50	0.2 nM
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
CHEMBL5286745	IC50	0.22 nM
CHEMBL3797579	IC50	0.24 nM
CHEMBL6168943	IC50	0.26 nM
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
CHEMBL4061378	IC50	0.3 nM
CHEMBL4104884	IC50	0.3 nM
CHEMBL2376640	IC50	0.32 nM
CHEMBL6152766	IC50	0.33 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
AP-26113	IC50	0.37 nM

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

3263 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
N-[3,5-difluoro-4-[6-[(2S)-1-hydroxypropan-2-yl]oxy-7-methoxyquinolin-4-yl]oxyphenyl]-4-methoxypyridine-3-carboxamide	2280066: Inhibition of N-terminal GST-tagged wild-type human c-MET (956 to 1390 residues) extracted from baculovirus infected Sf21 cells using 5-FAM-KKKKEEIYFFF-CONH2 as substrate preincubated for 30 mins followed by ATP addition measured after 60 mins by fluorescence-based microfluidic mobility shift assay	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
4-[3-[(7-methoxyquinolin-4-yl)oxymethyl]-[1,2,4]triazolo[4,3-b][1,2,4]triazin-6-yl]phenol	2236457: Inhibition of c-MET (unknown origin) incubated for 60 mins by ELISA analysis	ic50	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
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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Crizotinib	decreases response to substance, increases mutagenesis, decreases reaction, decreases phosphorylation, increases reaction (+7 more)	10
Valproic Acid	affects cotreatment, increases expression	7
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression, increases phosphorylation (+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	affects binding, decreases activity, decreases reaction, increases activity, increases phosphorylation (+4 more)	5
Quercetin	decreases expression, decreases reaction, affects binding, increases reaction, increases expression (+1 more)	4
Tretinoin	decreases expression, decreases reaction, increases expression	4
Resveratrol	decreases expression, increases expression, affects cotreatment	3
Benzo(a)pyrene	increases expression, decreases expression, decreases methylation	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	decreases reaction, increases phosphorylation, increases expression, affects reaction	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	affects cotreatment, decreases phosphorylation	2
Arsenic Trioxide	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	decreases expression, increases abundance, increases expression, affects cotreatment	2
Diclofenac	decreases expression, increases 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	affects cotreatment, decreases expression, decreases reaction, increases phosphorylation	2
Aflatoxin B1	decreases expression, decreases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases ubiquitination	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 expression, decreases phosphorylation	1
A-1155463	affects response to substance, decreases reaction, increases response to substance, affects reaction	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 327 trials:

NCT	Phase	Status	Title
NCT00414765	Phase 4	COMPLETED	Aldesleukin in Participants With Metastatic Renal Cell Carcinoma or Metastatic Melanoma
NCT00777504	Phase 4	UNKNOWN	Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors
NCT00930345	Phase 4	TERMINATED	Biological, Pathological and Imagery Markers in the First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma
NCT01206764	Phase 4	COMPLETED	A Trial of Everolimis in Patients With Advanced Renal Cell Carcinoma.
NCT01266837	Phase 4	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	Phase 4	COMPLETED	Everolimus in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
NCT02338570	Phase 4	TERMINATED	Outcome-related Factors in Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus (ORCHIDEE)
NCT02596035	Phase 4	COMPLETED	An Investigational Immuno-therapy Safety Trial of Nivolumab in Patients With Advanced or Metastatic Renal Cell Carcinoma
NCT02982954	Phase 4	COMPLETED	A Study to Evaluate the Safety of Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Cancer
NCT05949424	Phase 4	UNKNOWN	OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
NCT07028125	Phase 4	RECRUITING	Digital Monitoring of Self-reported Symptoms by Patients Treated With Cabozantinib Plus Nivolumab for Advanced Clear-cell Renal Carcinoma
NCT07405086	Phase 4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT05043090	Phase 3	ACTIVE_NOT_RECRUITING	Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic PRCC
NCT06146777	Phase 3	NOT_YET_RECRUITING	Multi-classifier System for Stratifying Stage III Papillary Renal Cell Carcinoma of Receiving Adjuvant Therapy
NCT00033904	Phase 3	COMPLETED	Survival Study Of Oncophage® vs. Observation In Patients With Kidney Cancer
NCT00126178	Phase 3	TERMINATED	Clinical Trial Studying a Personalized Cancer Vaccine in Patients With Non-metastatic Kidney Cancer
NCT00291369	Phase 3	COMPLETED	Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis
NCT00410124	Phase 3	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	Phase 3	COMPLETED	Temsirolimus Versus Sorafenib As Second-Line Therapy In Patients With Advanced RCC Who Have Failed First-Line Sunitinib
NCT00478114	Phase 3	COMPLETED	Efficacy and Safety of Sorafenib in Advanced Renal Cell Carcinoma (RCC)
NCT00606632	Phase 3	COMPLETED	Pre-surgical Detection of Clear Cell Renal Cell Carcinoma (ccRCC) Using Radiolabeled G250-Antibody
NCT00606866	Phase 3	COMPLETED	MRI Study of BAY 43-9006 in Metastatic Renal Cell Carcinoma
NCT00631371	Phase 3	COMPLETED	Study Comparing Bevacizumab + Temsirolimus vs. Bevacizumab + Interferon-Alfa In Advanced Renal Cell Carcinoma Subjects
NCT00732914	Phase 3	COMPLETED	Sequential Study to Treat Renal Cell Carcinoma
NCT00869011	Phase 3	UNKNOWN	Exercise for Patients With Renal Cell Cancer Receiving Sunitinib
NCT00930033	Phase 3	COMPLETED	Clinical Trial to Assess the Importance of Nephrectomy
NCT01030783	Phase 3	COMPLETED	A Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma
NCT01076010	Phase 3	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	Phase 3	TERMINATED	Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy
NCT01223027	Phase 3	COMPLETED	Study of Dovitinib Versus Sorafenib in Patients With Metastatic Renal Cell Carcinoma
NCT01224288	Phase 3	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	Phase 3	COMPLETED	A Study to Evaluate Pazopanib as an Adjuvant Treatment for Localized Renal Cell Carcinoma (RCC)
NCT01265810	Phase 3	COMPLETED	Caphosol in Oral Mucositis Due to Targeted Therapy
NCT01265901	Phase 3	COMPLETED	IMA901 in Patients Receiving Sunitinib for Advanced/Metastatic Renal Cell Carcinoma
NCT01481870	Phase 3	UNKNOWN	Comparison of Sequential Therapies With Sunitinib and Sorafenib in Advanced Renal Cell Carcinoma
NCT01582672	Phase 3	TERMINATED	Phase 3 Trial of Autologous Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma
NCT01613846	Phase 3	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	Phase 3	WITHDRAWN	REDECT 2: REnal Masses: Pivotal Trial to DEteCT Clear Cell Renal Cell Carcinoma With PET/CT
NCT01865747	Phase 3	COMPLETED	A Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma
NCT02231749	Phase 3	COMPLETED	Nivolumab Combined With Ipilimumab Versus Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 214)
NCT02420821	Phase 3	COMPLETED	A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma (RCC)
NCT02811861	Phase 3	ACTIVE_NOT_RECRUITING	Lenvatinib/Everolimus or Lenvatinib/Pembrolizumab Versus Sunitinib Alone as Treatment of Advanced Renal Cell Carcinoma
NCT02853331	Phase 3	COMPLETED	Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Axitinib Versus Sunitinib Monotherapy in Participants With Renal Cell Carcinoma (MK-3475-426/KEYNOTE-426)
NCT03024996	Phase 3	TERMINATED	A Study of Atezolizumab as Adjuvant Therapy in Participants With Renal Cell Carcinoma (RCC) at High Risk of Developing Metastasis Following Nephrectomy
NCT03055013	Phase 3	ACTIVE_NOT_RECRUITING	Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy
NCT03141177	Phase 3	COMPLETED	A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
NCT03142334	Phase 3	COMPLETED	Safety and Efficacy Study of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (MK-3475-564/KEYNOTE-564)
NCT03260894	Phase 3	COMPLETED	Pembrolizumab (MK-3475) Plus Epacadostat vs Standard of Care in mRCC (KEYNOTE-679/ECHO-302)
NCT03288532	Phase 3	RECRUITING	Renal Adjuvant MultiPle Arm Randomised Trial
NCT03408652	Phase 3	TERMINATED	Efficacy and Safety of Systemic Treatments of Bone Metastases From Kidney Cancer in Patients Treated With Targeted Therapies
NCT03592472	Phase 3	RECRUITING	A Study of Pazopanib With or Without Abexinostat in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma (RENAVIV)
NCT03693573	Phase 3	WITHDRAWN	A Study of Atezolizumab in Combination With Bevacizumab in Untreated Locally Advanced or Metastatic Clear Cell or Non-Clear Cell Renal Cell Carcinoma
NCT03729245	Phase 3	TERMINATED	A Study of Bempegaldesleukin (NKTR-214: BEMPEG) in Combination With Nivolumab Compared With the Investigator’s Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC)
NCT03873402	Phase 3	ACTIVE_NOT_RECRUITING	A Study of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Participants With Advanced Kidney Cancer
NCT03937219	Phase 3	ACTIVE_NOT_RECRUITING	Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
NCT04510597	Phase 3	RECRUITING	Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial
NCT04588246	Phase 3	TERMINATED	Comparing Whole Brain Radiotherapy Using a Technique That Avoids the Hippocampus to Stereotactic Radiosurgery in Patients With Cancer That Has Spread to the Brain and Come Back in Other Areas of the Brain After Earlier Stereotactic Radiosurgery
NCT04764487	Phase 3	UNKNOWN	A Web-mediated Follow-up With the Web-application KidneyPRO Versus Standard Follow-up for Patients With Advanced Renal Cell Carcinoma Treated With Axitinib/Pembrolizumab in First Line
NCT04987203	Phase 3	COMPLETED	Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma
NCT05078047	Phase 3	ACTIVE_NOT_RECRUITING	Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients in Response After 6 Months of Standard IO

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MET across ~30M SureChEMBL compounds — explore on Sugi Predict.