Protein / target

Hepatocyte growth factor receptor

METP08581Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
8
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Hepatocyte growth factor receptor activity

Primary system

Musculoskeletal system

Strongest disease association

papillary renal cell carcinoma

Genetic evidence · score 0.95

Therapeutic maturity

Clinically validated target

8 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

8 approved · 30 in clinical development

30 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from 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 (By similarity). 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 (By similarity)

Subcellular location

MembraneSecreted
Domains and Gene Ontology detail (34)

Domains & features

SemaIPT/TIG 1IPT/TIG 2IPT/TIG 3Protein kinase

Gene Ontology

  • Cbasal plasma membrane
  • Ccell surface
  • Cextracellular region
  • Cmembrane
  • Cplasma membrane
  • Cpostsynapse
  • Creceptor complex
  • FATP binding
  • Fhepatocyte growth factor receptor activity
  • Fidentical protein binding
  • Fmolecular function activator activity
  • Fprotein phosphatase binding

1390 aa · 156 kDa · 3 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Kinase signallingUniProt · GOSynaptic signallingGOExcitatory neurotransmissionGOImmune signallingReactomeCell adhesionUniProtTranscriptional regulationGO
View supporting evidence

Kinase signalling

  • ·Receptor tyrosine kinase that transduces signals from the extracellular matrix into the…
  • ·protein tyrosine kinase activity

Synaptic signalling

  • ·postsynapse
  • ·excitatory postsynaptic potential

Excitatory neurotransmission

  • ·excitatory postsynaptic potential

Immune signalling

  • ·InlB-mediated entry of Listeria monocytogenes into host cell

Cell adhesion

  • ·Receptor tyrosine kinase that transduces signals from the extracellular matrix into the…

Transcriptional regulation

  • ·positive regulation of transcription by RNA polymerase II
View underlying pathways (19)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

HGFCBLGRB2PLXNB1EGFRCD44SRCSHC1GAB1ERBB3MET

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

4

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

amivantamab
Narrow target profileApprovedInhibitor

Hepatocyte growth factor receptor inhibitor

Appears in clinical studies involving non-small cell lung carcinoma, non-small cell lung carcinoma, non-small cell lung carcinoma, neoplasm

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

tepotinib
Narrow target profileApprovedInhibitor

Hepatocyte growth factor receptor inhibitor

Appears in clinical studies involving non-small cell lung carcinoma, non-small cell lung carcinoma, neoplasm, non-small cell lung carcinoma

Direct interaction with this protein · Only this protein recorded as a target

crizotinib
ApprovedInhibitor

Hepatocyte growth factor receptor inhibitor

Appears in clinical studies involving non-small cell lung carcinoma, non-small cell lung carcinoma, non-small cell lung carcinoma, neoplasm

Direct interaction with this protein · 1 of 6 recorded protein targets

telisotuzumab vedotin
Phase 3Binding agent

Hepatocyte growth factor receptor binding agent

Appears in clinical studies involving non-small cell lung carcinoma, non-small cell lung carcinoma, squamous cell lung carcinoma, squamous cell carcinoma

Direct interaction with this protein · 1 of 16 recorded protein targets — broad pharmacology

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

papillary renal cell carcinoma0.95

Genetic · overall 0.83

Inherited cancer-predisposing syndrome0.87

Genetic · overall 0.53

hereditary neoplastic syndrome0.87

Genetic · overall 0.53

hereditary papillary renal cell carcinoma0.86

Genetic · overall 0.77

renal cell carcinoma0.84

Genetic · overall 0.73

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

non-small cell lung carcinoma0.99

Clinical · overall 0.72

neoplasm0.90

Clinical · overall 0.63

hepatocellular carcinoma0.88

Clinical · overall 0.76

medullary thyroid gland carcinoma0.84

Clinical · overall 0.59

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

listeriosis0.57

Pathway

Show all associations
papillary renal cell carcinoma0.83
hereditary papillary renal cell carcinoma0.77
hepatocellular carcinoma0.76
renal cell carcinoma0.73
non-small cell lung carcinoma0.72
neoplasm0.63
medullary thyroid gland carcinoma0.59
listeriosis0.57
Inherited cancer-predisposing syndrome0.53
hereditary neoplastic syndrome0.53

Open Targets ranks 2,315 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 38 total

SGX-523Phase 1

cancer · cancer

FORETINIBPhase 2

breast cancer · gastric adenocarcinoma · renal cell carcinoma

TELISOTUZUMABPhase 1

neoplasm

SAVOLITINIBPhase 3

renal cell carcinoma · papillary renal cell carcinoma · non-small cell lung carcinoma

TELISOTUZUMAB VEDOTINPhase 3

non-small cell lung carcinoma · non-small cell lung carcinoma · squamous cell lung carcinoma

MERESTINIBPhase 2

biliary tract cancer · non-small cell lung carcinoma · rectum adenocarcinoma

TEPOTINIBApproval

non-small cell lung carcinoma · non-small cell lung carcinoma · neoplasm

CRIZOTINIBApproval

non-small cell lung carcinoma · non-small cell lung carcinoma · non-small cell lung carcinoma

BPI-9016Phase 1

neoplasm · non-small cell lung carcinoma

ONARTUZUMABPhase 3

non-small cell lung carcinoma · gastric adenocarcinoma · gastroesophageal junction adenocarcinoma

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · Approved DrugAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · LiteraturePR · UniProt Ubiquitination

Safety liabilities

regulation of catalytic activity

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

Show remaining trials (24)

ACTIVE_NOT_RECRUITING · via amivantamab · NCT05117931

ACTIVE_NOT_RECRUITING · via crizotinib · NCT02465060

ACTIVE_NOT_RECRUITING · via crizotinib · NCT06357975

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

papillary renal cell carcinomaWell supported
0.98
agreement 0.891.00
Genetic51%Clinical23%Somatic mutation21%Literature3%RNA expression2%Genetic literaturedup

Open Targets aggregate 0.83 · 5 independent evidence families · 1 not counted as duplicate

hepatocellular carcinomaWell supported
0.98
agreement 0.901.00
Genetic34%Clinical27%Somatic mutation12%Animal model10%Pathway10%Literature6%Genetic literaturedup

Open Targets aggregate 0.76 · 6 independent evidence families · 1 not counted as duplicate

renal cell carcinomaWell supported
0.97
agreement 0.871.00
Genetic45%Clinical37%Somatic mutation10%Literature7%

Open Targets aggregate 0.73 · 4 independent evidence families

hereditary papillary renal cell carcinomaWell supported
0.89
agreement 0.771.00
Genetic80%Animal model19%Literature2%Genetic literaturedup

Open Targets aggregate 0.77 · 3 independent evidence families · 1 not counted as duplicate

non-small cell lung carcinomaWell supported
0.89
agreement 0.780.99
Clinical51%Somatic mutation20%Pathway19%Literature10%

Open Targets aggregate 0.72 · 4 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

12

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 4 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. New publication2024-06-26
    Amivantamab plus Lazertinib in Previously Untreated <i>EGFR</i>-Mutated Advanced NSCLC.

    The New England journal of medicine · 2024 · 303 citations · Europe PMC · via amivantamab

  2. New publication2024-06-06
    Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Nonsquamous &lt;i&gt;EGFR&lt;/i&gt;-Wildtype Non-Small Cell Lung Cancer in the Phase II LUMINOSITY Trial.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024 · 113 citations · Europe PMC · via telisotuzumab vedotin

  3. New publication2024-05-31
    Lorlatinib Versus Crizotinib in Patients With Advanced &lt;i&gt;ALK&lt;/i&gt;-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024 · 254 citations · Europe PMC · via crizotinib

  4. Regulatory approval2022-02-16

    Approval: Tepmetko (EMA)

    ema · regulatory · ema · via tepotinib

  5. Regulatory approval2021-12-09

    Approval: Rybrevant (EMA)

    ema · regulatory · ema · via amivantamab

  6. New publication2021-09-16
    Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial.

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2021 · 300 citations · Europe PMC · via crizotinib

  7. New publication2021-08-02
    Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021 · 499 citations · Europe PMC · via amivantamab

  8. New publication2020-05-29
    Tepotinib in Non-Small-Cell Lung Cancer with <i>MET</i> Exon 14 Skipping Mutations.

    The New England journal of medicine · 2020 · 653 citations · Europe PMC · via tepotinib

  9. Safety communication2015-11-12

    Drug Safety Update: Crizotinib (Xalkori▼): risk of cardiac failure

    mhra · safety · mhra · via crizotinib

  10. New publication2014-12-01
    First-line crizotinib versus chemotherapy in ALK-positive lung cancer.

    The New England journal of medicine · 2014 · 2,470 citations · Europe PMC · via crizotinib

  11. Regulatory approval2012-10-23

    Approval: Xalkori (EMA)

    ema · regulatory · ema · via crizotinib

  12. New publication2012-01-03
    ROS1 rearrangements define a unique molecular class of lung cancers.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2012 · 1,121 citations · Europe PMC · via crizotinib

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.