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Protein / target

Proto-oncogene tyrosine-protein kinase ROS

Encoded byROS1P08922Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Transmembrane receptor protein tyrosine kinase

Strongest disease association

Lung carcinoma

Via encoding gene ROS1 · Genetic evidence · score 0.44

Therapeutic position

Established drug target

Small molecules

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 (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium.

View complete UniProt function annotation

Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. NELL2 is an endogenous ligand for ROS1. Upon endogenous stimulation by NELL2, ROS1 activates the intracellular signaling pathway and triggers epididymal epithelial differentiation and subsequent sperm maturation (By similarity). May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. Mediates the phosphorylation of PTPN11, an activator of this pathway. May also phosphorylate and activate the transcription factor STAT3 to control anchorage-independent cell growth. Mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. May activate other downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1 and PLCG2

Subcellular location

Cell membrane
Domains and Gene Ontology detail (25)

Domains & features

Fibronectin type-III 1Fibronectin type-III 2Fibronectin type-III 3Fibronectin type-III 4Fibronectin type-III 5Fibronectin type-III 6Fibronectin type-III 7Fibronectin type-III 8Fibronectin type-III 9Protein kinase

Gene Ontology

  • Cmembrane
  • Cplasma membrane
  • Creceptor complex
  • FATP binding
  • Fprotein phosphatase binding
  • Fprotein tyrosine kinase activity
  • Ftransmembrane receptor protein tyrosine kinase activity
  • Pcell differentiation
  • Pcell surface receptor protein tyrosine kinase signaling pathway
  • Pcolumnar/cuboidal epithelial cell development
  • Pprotein phosphorylation
  • Pregulation of cell growth

2347 aa · 264 kDa

Biological roles

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

Receptor tyrosine kinase signallingUniProt · GO
View supporting evidence

Receptor tyrosine kinase signalling

  • ·Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and…
  • ·transmembrane receptor protein tyrosine kinase activity
  • ·cell surface receptor protein tyrosine kinase signaling pathway

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.

EML4OR13G1TAS2R50GOPCKRASPALLDSLC34A2CCDC6CD74TPM3ROS1

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

3 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

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

3

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.

crizotinib
ApprovedInhibitor

Proto-oncogene tyrosine-protein kinase ROS inhibitor

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

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

repotrectinib
ApprovedInhibitor

Proto-oncogene tyrosine-protein kinase ROS inhibitor

Indicated for Neoplasms

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

entrectinib
ApprovedInhibitor

Proto-oncogene tyrosine-protein kinase ROS inhibitor

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

Direct interaction with this protein · 1 of 5 recorded protein targets

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 ROS1

Gene-level evidence surfaced through the gene ROS1that 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, Non-Small-Cell Lung
0.90Well supported

Clinical evidence dominant · Open Targets 0.71

Adenocarcinoma of Lung
0.83Well supported

Somatic mutation evidence dominant · Open Targets 0.59

Neoplasms
0.82Well supported

Clinical evidence dominant · Open Targets 0.60

Lung carcinoma
0.72Moderately supported

Genetic evidence dominant · Open Targets 0.45

Melanoma
0.51Moderately supported

Somatic mutation evidence dominant · Open Targets 0.40

View evidence synthesis (5)
Carcinoma, Non-Small-Cell LungWell supported
0.90
agreement 0.791.00
Clinical48%Somatic mutation26%Pathway16%Literature10%

Open Targets aggregate 0.71 · 4 independent evidence families

Adenocarcinoma of LungWell supported
0.83
agreement 0.750.91
Somatic mutation33%Genetic27%Pathway26%Clinical8%Literature6%RNA expression0%

Open Targets aggregate 0.59 · 6 independent evidence families

NeoplasmsWell supported
0.82
agreement 0.730.91
Clinical53%Genetic20%Somatic mutation16%Literature11%

Open Targets aggregate 0.60 · 4 independent evidence families

Lung carcinomaModerately supported
0.72
agreement 0.610.82
Genetic44%Somatic mutation40%Literature9%RNA expression8%

Open Targets aggregate 0.45 · 4 independent evidence families

MelanomaModerately supported
0.51
agreement 0.390.63
Somatic mutation67%Literature17%Clinical16%

Open Targets aggregate 0.40 · 3 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, Non-Small-Cell Lung0.71
Neoplasms0.60
Adenocarcinoma of Lung0.59
Lung carcinoma0.45
Melanoma0.40
Squamous cell lung carcinoma0.39
Cutaneous melanoma0.38
Spitz nevus0.37
Melanocytic neoplasm0.37

Drug development

4 compounds recorded · 3 approved · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 3 drugs that target this protein in Forefront's canonical graph (3 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (4)
CRIZOTINIBApproval
ENTRECTINIBApproval
TALETRECTINIBPhase 3
REPOTRECTINIBApproval

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.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and uniprot sigp or tmhmm) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · UniProt SigP or TMHMMAB · GO CC med confPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

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

9

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 3 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. Regulatory approval2025-01-13

    Approval: Augtyro (EMA)

    ema · regulatory · ema · via repotrectinib

  2. 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

  3. New publication2024-01-01
    Repotrectinib in <i>ROS1</i> Fusion-Positive Non-Small-Cell Lung Cancer.

    The New England journal of medicine · 2024 · 168 citations · Europe PMC · via repotrectinib

  4. 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

  5. Regulatory approval2020-07-31

    Approval: Rozlytrek (EMA)

    ema · regulatory · ema · via entrectinib

  6. Safety communication2015-11-12

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

    mhra · safety · mhra · via crizotinib

  7. 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

  8. Regulatory approval2012-10-23

    Approval: Xalkori (EMA)

    ema · regulatory · ema · via crizotinib

  9. 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.