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.

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

1 medicine · 1 area

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.

Neoplasms1 medicine

repotrectinib

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

Drugs targeting this protein

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.

repotrectinib

ApprovedInhibitor

ROS1-SDC4 inhibitor

Indicated for Neoplasms

Direct interaction with this protein · 1 of 6 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 SDC4

Gene-level evidence surfaced through the gene SDC4that 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

0.79Well supported

Clinical evidence dominant · Open Targets 0.62

Neoplasms

0.53Moderately supported

Clinical evidence dominant · Open Targets 0.40

Adenocarcinoma of Lung

0.41Limited support

Somatic mutation evidence dominant · Open Targets 0.37

Acinar lung adenocarcinoma

0.40Limited support

Somatic mutation evidence dominant · Open Targets 0.37

COVID-19

0.36Preliminary

Pathway evidence dominant · Open Targets 0.54 · no direct causal or clinical evidence

View evidence synthesis (5)

Carcinoma, Non-Small-Cell LungWell supported

0.79

agreement 0.67–0.91

Clinical61%Somatic mutation37%Literature2%

Open Targets aggregate 0.62 · 3 independent evidence families

NeoplasmsModerately supported

0.53

agreement 0.37–0.68

Clinical77%Literature23%

Open Targets aggregate 0.40 · 2 independent evidence families

Adenocarcinoma of LungLimited support

0.41

agreement 0.27–0.55

Somatic mutation94%Literature5%RNA expression1%

Open Targets aggregate 0.37 · 3 independent evidence families

Acinar lung adenocarcinomaLimited support

0.40

agreement 0.21–0.58

Somatic mutation100%

Open Targets aggregate 0.37 · 1 independent evidence family

COVID-19Preliminary

0.36

agreement 0.18–0.54

Pathway98%Literature2%

Open Targets aggregate 0.54 · 2 independent evidence families · no direct causal or clinical evidence

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 Lung0.62

COVID-190.54

Dengue0.46

Neoplasms0.40

Adenocarcinoma of Lung0.37

Acinar lung adenocarcinoma0.37

Gastric adenocarcinoma0.28

Neurodegenerative Diseases0.28

Signet ring cell gastric adenocarcinoma0.28

Drug development

1 compounds recorded · 1 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (1)

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 molecules — Strong

Approved Drug support this modality.

Antibodies — Emerging

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

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)

SM · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Database UbiquitinationPR · Half-life Data

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

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.

Randomized, Open-label, Multicenter, Phase 3 Trial of Repotrectinib Versus Crizotinib in Participants With Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3)PHASE3

ACTIVE_NOT_RECRUITING · via repotrectinib · NCT06140836

A Phase II Study Assessing Safety and Efficacy of REPotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain mEtastasis (REPOSE Study)PHASE2

RECRUITING · via repotrectinib · NCT06315010

Open-label Phase II Efficacy Study of Repotrectinib in Frail (PS ≥2) and/or Elderly Patients With ROS1-rearranged Advanced NSCLCPHASE2

RECRUITING · via repotrectinib · NCT06552234

Phase 1/2 Study of TPX-0005 (Repotrectinib) in Combination With Chemotherapy in Pediatric and Young Adult Subjects With Advanced or Metastatic Solid Tumors and Primary Central Nervous System TumorsPHASE1/PHASE2

RECRUITING · via repotrectinib · NCT05004116

View all trials (8)

A Phase 1/2, Open-Label, Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity Study of Repotrectinib in Pediatric and Young Adult Subjects With Advanced or Metastatic Malignancies Harboring ALK, ROS1, NTRK1-3 AlterationsPHASE1/PHASE2

RECRUITING · via repotrectinib · NCT04094610

A Phase 1/2, Open-Label, Multi-Center, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of TPX-0005 in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)PHASE1/PHASE2

RECRUITING · via repotrectinib · NCT03093116

Phase II Study of REPotrectinib With or Without Fulvestrant in Patients With Hormone Receptor-positive Human Epidermal Growth Factor 2-negative Metastatic Invasive LObular Carcinoma Who Received a Prior Endocrine Therapy in Combination With Cyclin-dependent Kinase 4 and 6 Inhibitor (REPLOT Trial)PHASE2

TERMINATED · via repotrectinib · NCT06408168

Phase 1, 2-Cohort, Open-label, Fixed-sequence, Drug-drug Interaction Study to Evaluate the Effect of Repotrectinib on the Pharmacokinetics of Transporter and CYP P450 Probe Substrates in Healthy Adult ParticipantsPHASE1

COMPLETED · via repotrectinib · NCT07223671

A Phase I, Two-part, Single-center, Open-label, Drug-drug Interaction Study to Assess the Effect of Voriconazole (Part 1) and Quinidine (Part 2) on the Pharmacokinetics of a Single Dose of Repotrectinib (BMS-986472) in Healthy ParticipantsPHASE1

COMPLETED · via repotrectinib · NCT06493409

A Phase 1, Multicenter, Open-label, Single-dose Study to Assess the Pharmacokinetics of Repotrectinib in Healthy Participants and Those With Moderate and Severe Hepatic ImpairmentPHASE1

COMPLETED · via repotrectinib · NCT06352528

A Phase 1 Study to Assess the Effect of Hepatic Impairment on the Pharmacokinetics of Repotrectinib in Advanced Cancer PatientsPHASE1

WITHDRAWN · via repotrectinib · NCT05828277

Phase I Clinical Study to Assess Safety and Efficacy of Repotrectinib Combined With Osimertinib in Patients With Advanced, Metastatic EGFR Mutant NSCLC (TOTEM).PHASE1

UNKNOWN · via repotrectinib · NCT04772235

ClinicalTrials.gov via the drug-target graph.

What's happening now

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets 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.

Regulatory approval2025-01-13
Approval: Augtyro (EMA)
ema · regulatory · ema · via repotrectinib
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

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.