Protein / target

Macrophage-stimulating protein receptor

MST1RQ04912Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Phase 1 Clinical

Protein at a glance

Biological role

Transmembrane receptor protein tyrosine kinase activity

Primary system

Immune system

Strongest disease association

nasopharyngeal neoplasm

Genetic evidence · score 0.87

Therapeutic maturity

Clinically validated target

1 approved medicine against this target

Druggability

Small molecule

Open Targets tractability · Phase 1 Clinical

Clinical development

1 approved · 3 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 MST1 ligand. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces autophosphorylation of RON on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. Recruitment of these downstream effectors by RON leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. Also plays a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Alternatively, RON can also promote signals such as cell migration and proliferation in response to growth factors other than MST1 ligand

Subcellular location

Membrane
Domains and Gene Ontology detail (26)

Domains & features

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

Gene Ontology

  • Ccell surface
  • Cplasma membrane
  • Creceptor complex
  • Cstress fiber
  • Cvacuole
  • FATP binding
  • Fenzyme binding
  • Fmacrophage colony-stimulating factor receptor activity
  • Ftransmembrane receptor protein tyrosine kinase activity
  • Pcell migration
  • Pcell surface receptor protein tyrosine kinase signaling pathway
  • Pdefense response

1400 aa · 152 kDa · 7 isoforms

Biological roles

Reactome v97

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

Kinase signallingUniProt · GOImmune signallingUniProt · GOCell adhesionUniProt
View supporting evidence

Kinase signalling

  • ·Receptor tyrosine kinase that transduces signals from the extracellular matrix into the…
  • ·transmembrane receptor protein tyrosine kinase activity
  • ·positive regulation of MAP kinase activity
  • ·positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction

Immune signalling

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

Cell adhesion

  • ·Receptor tyrosine kinase that transduces signals from the extracellular matrix into the…
View underlying pathways (1)

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.

MST1HGFHYAL2CBLSRSF1SPAM1EGFRCTNNB1GRB2PLXNB1MST1R

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

1

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.

crizotinib
ApprovedInhibitor

Macrophage-stimulating protein 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

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.

nasopharyngeal neoplasm0.87

Genetic · overall 0.62

nasopharyngeal carcinoma0.35

Genetic · overall 0.23

Abnormality of the skeletal system0.26

Genetic · overall 0.16

diabetes mellitus0.25

Genetic · overall 0.15

Highest-confidence therapeutic associations

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

non-small cell lung carcinoma0.95

Clinical · overall 0.59

neoplasm0.62

Clinical · overall 0.41

cancer0.48

Clinical · overall 0.32

non-small cell squamous lung carcinoma0.46

Clinical · overall 0.28

inflammatory myofibroblastic tumor0.33

Clinical · overall 0.20

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

uveal melanoma0.20

Clinical

Show all associations
nasopharyngeal neoplasm0.62
non-small cell lung carcinoma0.59
neoplasm0.41
cancer0.32
non-small cell squamous lung carcinoma0.28
nasopharyngeal carcinoma0.23
inflammatory myofibroblastic tumor0.20
uveal melanoma0.20
Abnormality of the skeletal system0.16
diabetes mellitus0.15

Open Targets ranks 354 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 · 4 total

NARNATUMABPhase 1
CRIZOTINIBApproval

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

GLESATINIBPhase 2

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

MK-8033Phase 1

Tractability

SM · Phase 1 ClinicalSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · Advanced ClinicalAB · GO CC high confAB · UniProt SigP or TMHMMPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

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 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.

nasopharyngeal neoplasmWell supported
0.86
agreement 0.740.98
Genetic100%Genetic literaturedup

Open Targets aggregate 0.62 · 1 independent evidence family · 1 not counted as duplicate

non-small cell lung carcinomaModerately supported
0.74
agreement 0.580.89
Clinical89%Literature11%

Open Targets aggregate 0.59 · 2 independent evidence families

neoplasmModerately supported
0.54
agreement 0.390.70
Clinical76%Literature24%

Open Targets aggregate 0.41 · 2 independent evidence families

cancerLimited support
0.45
agreement 0.290.60
Clinical73%Literature27%

Open Targets aggregate 0.32 · 2 independent evidence families

nasopharyngeal carcinomaLimited support
0.39
agreement 0.250.53
Genetic87%Literature13%

Open Targets aggregate 0.23 · 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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

6

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

  1. New publication2024-05-31
    Lorlatinib Versus Crizotinib in Patients With Advanced <i>ALK</i>-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

  2. 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

  3. Safety communication2015-11-12

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

    mhra · safety · mhra · via crizotinib

  4. 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

  5. Regulatory approval2012-10-23

    Approval: Xalkori (EMA)

    ema · regulatory · ema · via crizotinib

  6. 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.