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Protein / target

Hepatocyte growth factor receptor

Encoded byMETP08581Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
8
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Hepatocyte growth factor receptor

Strongest disease association

Carcinoma, Renal Cell

Via encoding gene MET · Genetic evidence · score 0.95

Therapeutic position

Established drug target

Small molecules and antibodies

Research activity

Emerging research

3 papers · latest 2024

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 overview

Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand.

View complete UniProt function annotation

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.

Receptor tyrosine kinase signallingUniProt · GOCell proliferation & survivalReactomeCell migrationGOExcitatory neurotransmissionGOGrowth-factor signallingGOOncogenic signallingReactome
View supporting evidence

Receptor tyrosine kinase signalling

  • ·Receptor tyrosine kinase that transduces signals from the extracellular matrix into the…
  • ·cell surface receptor protein tyrosine kinase signaling pathway

Cell proliferation & survival

  • ·PIP3 activates AKT signaling
  • ·PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
  • ·MET activates PI3K/AKT signaling

Cell migration

  • ·positive chemotaxis
  • ·positive regulation of endothelial cell chemotaxis

Excitatory neurotransmission

  • ·excitatory postsynaptic potential

Growth-factor signalling

  • ·hepatocyte growth factor receptor signaling pathway

Oncogenic signalling

  • ·Constitutive Signaling by Aberrant PI3K in Cancer
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.

Approved medicines with mapped indications

4 medicines · 2 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Carcinoma, Non-Small-Cell Lung2 medicines

8 medicines meet Open Targets' target-level approved-medicine definition; the 4 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

5

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

amivantamab
Narrow target profileApprovedInhibitor

Hepatocyte growth factor receptor inhibitor

Indicated for Carcinoma, Non-Small-Cell Lung, Neoplasms

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

tepotinib
Narrow target profileApprovedInhibitor

Hepatocyte growth factor receptor inhibitor

Indicated for Neoplasms

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

capmatinib
Narrow target profileApprovedInhibitor

Hepatocyte growth factor receptor inhibitor

Indicated for Neoplasms

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

crizotinib
ApprovedInhibitor

Hepatocyte growth factor receptor inhibitor

Indicated for Carcinoma, Non-Small-Cell Lung, Neoplasms

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

telisotuzumab vedotin
Phase 3Binding agent

Hepatocyte growth factor receptor binding agent

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene MET

Gene-level evidence surfaced through the gene METthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Carcinoma, Renal Cell
0.99Well supported

Genetic evidence dominant · Open Targets 0.83

Carcinoma, Hepatocellular
0.98Well supported

Genetic evidence dominant · Open Targets 0.76

Hereditary papillary renal cell carcinoma
0.89Well supported

Genetic evidence dominant · Open Targets 0.77

Carcinoma, Non-Small-Cell Lung
0.89Well supported

Clinical evidence dominant · Open Targets 0.72

Inherited cancer-predisposing syndrome
0.87Well supported

Genetic evidence dominant · Open Targets 0.53

View evidence synthesis (5)
Carcinoma, Renal CellWell supported
0.99
agreement 0.901.00
Genetic43%Clinical32%Somatic mutation18%Literature6%RNA expression2%Genetic literaturedup

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

Carcinoma, HepatocellularWell 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

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

Carcinoma, Non-Small-Cell LungWell supported
0.89
agreement 0.780.99
Clinical51%Somatic mutation20%Pathway19%Literature10%

Open Targets aggregate 0.72 · 4 independent evidence families

Inherited cancer-predisposing syndromeWell supported
0.87
agreement 0.731.00
Genetic99%Literature1%

Open Targets aggregate 0.53 · 2 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 per-type scores above show the calculation.

Show all associations
Carcinoma, Renal Cell0.83
Hereditary papillary renal cell carcinoma0.77
Carcinoma, Hepatocellular0.76
Carcinoma, Non-Small-Cell Lung0.72
Neoplasms0.63
Medullary thyroid gland carcinoma0.59
Listeriosis0.57
Inherited cancer-predisposing syndrome0.53
Neoplastic Syndromes, Hereditary0.53

Drug development

38 compounds recorded · 8 approved · 30 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 5 drugs that target this protein in Forefront's canonical graph (4 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
SGX-523Phase 1
FORETINIBPhase 2
TELISOTUZUMABPhase 1
SAVOLITINIBPhase 3
TELISOTUZUMAB VEDOTINPhase 3
MERESTINIBPhase 2
TEPOTINIBApproval
CRIZOTINIBApproval
BPI-9016Phase 1
ONARTUZUMABPhase 3

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesStrong

Approved Drug and GO CC high conf support this modality.

Protein degradersEmerging

Feasibility evidence (literature and uniprot ubiquitination) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (16)
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 UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of catalytic activityToxCast

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 4 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  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.

Research activity

3 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Recent

Europe PMC papers linked directly to this protein.