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Repotrectinib

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Also known as AugtyroTPX-0005TRX-0005NA

Summary

Repotrectinib (CHEMBL4298138) is an approved small-molecule EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor (ATC L01EX28) targeting NTRK1, NTRK2, and NTRK3; indicated across 4 conditions including neoplasm and non-small cell lung carcinoma; with CIViC clinical evidence for 8 variant-indication associations (e.g. ROS1 Fusion in lung non-small cell carcinoma).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01EX28
  • Targets: 6 (NTRK1, NTRK2, NTRK3…)
  • Indications: 4 conditions
  • Clinical trials: 16
  • Precision-oncology evidence (CIViC): 8 variant–indication associations
  • Chemistry: 355.4 Da · C18H18FN5O2

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL4298138
NameRepotrectinib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID135565923
ChEBICHEBI:229220
ATCL01EX28
Molecular formulaC18H18FN5O2
Molecular weight355.4
InChIKeyFIKPXCOQUIZNHB-WDEREUQCSA-N

SMILES: C[C@H]1CNC(=O)C2=C3N=C(C=CN3N=C2)N[C@@H](C4=C(O1)C=CC(=C4)F)C

IUPAC name: (3R,11S)-6-fluoro-3,11-dimethyl-10-oxa-2,13,17,18,21-pentazatetracyclo[13.5.2.04,9.018,22]docosa-1(21),4(9),5,7,15(22),16,19-heptaen-14-one

ChEBI definition: An azamacrocycle with formula C18H18FN5O2. It is a tyrosine kinase inhibitor (highly potent against ROS1, TRKA-C, and ALK) used for the treatment of locally advanced or metastatic ROS1-positive non-small cell lung cancer.

Pharmacological roles (ChEBI): EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor, antineoplastic agent.

Also known as: Augtyro, Repotrectinib, TPX-0005, TRX-0005, REPOTRECTINIB, NA

Patent coverage: 405 distinct patent families (1,038 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 957 (92%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
NTRK1neurotrophic receptor tyrosine kinase 1Inhibition9.280.1%P04629
NTRK2neurotrophic receptor tyrosine kinase 2Inhibition9.520%Q16620
NTRK3neurotrophic receptor tyrosine kinase 3Inhibition9.680%Q16288
ALKALK receptor tyrosine kinaseInhibition8.980.8%Q9UM73
ROS1c-ros oncogene 1, receptor tyrosine kinaseInhibition10.150.1%P08922
JAK2Janus kinase 2Inhibition8.980.7%O60674

Broader ChEMBL bioactivity targets: 14 (assay-derived). Sample: Proto-oncogene tyrosine-protein kinase Src, Focal adhesion kinase 1, High affinity nerve growth factor receptor, Cytochrome P450 2D6, Tyrosine-protein kinase JAK2, Cytochrome P450 2C9, Cytochrome P450 2C19, EML4-ALK, ALK tyrosine kinase receptor, SLC34A2-ROS1.

Bioactivity

ChEMBL activities: 79 potent at pChembl ≥ 5 of 81 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
NTRK311IC500.01nMCHEMBL_ACT_24364049
NTRK210.3IC500.05nMCHEMBL_ACT_24364239
NTRK210.3IC500.05nMCHEMBL_ACT_25611322
NTRK210.3IC500.05nMCHEMBL_ACT_25905432
NTRK210.3IC500.05nMCHEMBL_ACT_29055473
NTRK210.3IC500.05nMCHEMBL_ACT_29077898
ROS110.15IC500.07nMCHEMBL_ACT_24364241
ROS110.15IC500.07nMCHEMBL_ACT_25905430
ROS110.15IC500.07nMCHEMBL_ACT_26182612
ROS110.15IC500.07nMCHEMBL_ACT_29055471
ROS110.15IC500.07nMCHEMBL_ACT_29077896
JAK210.09Kd0.08nMCHEMBL_ACT_27508418
JAK210.09Kd0.08nMCHEMBL_ACT_27936212
NTRK310IC500.1nMCHEMBL_ACT_24364240
NTRK310IC500.1nMCHEMBL_ACT_25611324
NTRK310IC500.1nMCHEMBL_ACT_25905433
NTRK310IC500.1nMCHEMBL_ACT_29055474
NTRK310IC500.1nMCHEMBL_ACT_29077899
NTRK19.96IC500.11nMCHEMBL_ACT_24503910
ROS19.77IC500.17nMCHEMBL_ACT_24364059
NTRK19.7IC500.2nMCHEMBL_ACT_24365554
NTRK19.4IC500.4nMCHEMBL_ACT_18946691
NTRK19.32IC500.48nMCHEMBL_ACT_24843608
NTRK19.3IC500.5nMCHEMBL_ACT_26045842
CD749.15IC500.7nMCHEMBL_ACT_29238081
SLC34A29.1IC500.8nMCHEMBL_ACT_29238049
NTRK19.08IC500.83nMCHEMBL_ACT_24364022
NTRK19.08IC500.83nMCHEMBL_ACT_25611319
NTRK19.08IC500.83nMCHEMBL_ACT_25905431
NTRK19.08IC500.83nMCHEMBL_ACT_26182606

Target pathways

Aggregated over 6 target gene(s): NTRK1, NTRK2, NTRK3, ALK, ROS1, JAK2.

Top Reactome pathways

109 total, by targets touching each:

PathwayTargetsGenes
PIP3 activates AKT signaling2NTRK2, NTRK3
Signal Transduction2ALK, JAK2
Disease2ALK, JAK2
NGF-independant TRKA activation2NTRK1, NTRK2
Constitutive Signaling by Aberrant PI3K in Cancer2NTRK2, NTRK3
Diseases of signal transduction by growth factor receptors and second messengers2ALK, JAK2
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling2NTRK2, NTRK3
Signaling by Receptor Tyrosine Kinases2ALK, JAK2
Interleukin-6 signaling1JAK2
Hemostasis1JAK2
MAPK3 (ERK1) activation1JAK2
RAF-independent MAPK1/3 activation1JAK2
MAPK1 (ERK2) activation1JAK2
Prolactin receptor signaling1JAK2
Cytokine Signaling in Immune system1JAK2
Signaling by SCF-KIT1JAK2
Cell Cycle1JAK2
PLC-gamma1 signalling1NTRK1
Signalling to RAS1NTRK1
Immune System1JAK2
Frs2-mediated activation1NTRK1
ARMS-mediated activation1NTRK1
Retrograde neurotrophin signalling1NTRK1
TRKA activation by NGF1NTRK1
Signalling to p38 via RIT and RIN1NTRK1
PI3K/AKT activation1NTRK1
Signalling to STAT31NTRK1
Signaling by ALK1ALK
Signaling by Leptin1JAK2
RMTs methylate histone arginines1JAK2

Dominant GO biological processes

GO termTargets
protein phosphorylation6
cell surface receptor protein tyrosine kinase signaling pathway5
cell differentiation5
protein autophosphorylation4
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction4
nervous system development4
circadian rhythm3
positive regulation of neuron projection development3
mechanoreceptor differentiation3
negative regulation of neuron apoptotic process3
positive regulation of synapse assembly3
positive regulation of cell population proliferation3
positive regulation of MAPK cascade3
signal transduction3
spermatogenesis2

Indications & clinical

Indications

4 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
neoplasm4MONDO:0005070EFO:0000616
non-small cell lung carcinoma3MONDO:0005233EFO:0003060
liver disorder1MONDO:0005154EFO:0001421

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 16.

Phase distribution

PhaseTrials
PHASE16
PHASE1/PHASE24
PHASE23
Not specified2
PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT06140836PHASE3ACTIVE_NOT_RECRUITINGA Study 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)
NCT03093116PHASE1/PHASE2RECRUITINGA Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements
NCT04094610PHASE1/PHASE2RECRUITINGA Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
NCT05004116PHASE1/PHASE2RECRUITINGA Study of Repotrectinib in Combination With Chemotherapy in Children and Young Adults With Solid Tumor Cancer
NCT06315010PHASE2RECRUITINGREPotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain mEtastasis
NCT06552234PHASE2RECRUITINGPhase II Efficacy Study of Repotrectinib in Frail and/or Elderly Patients With ROS1-rearranged Advanced NSCLC
NCT05071183PHASE1/PHASE2TERMINATEDA Study of Repotrectinib in Combination With Other Anticancer Therapies for the Treatment of Subjects With KRAS-Mutant Solid Tumors
NCT06408168PHASE2TERMINATEDPhase 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)
NCT04772235PHASE1RECRUITINGPhase I Study of Repotrectinib and Osimertinib in NSCLC Patients
NCT05828277PHASE1WITHDRAWNA Phase 1 Study to Assess the Effect of Hepatic Impairment on the Pharmacokinetics of Repotrectinib in Advanced Cancer Patients
NCT05828303PHASE1WITHDRAWNA Phase 1 Study to Evaluate the Potential Drug Interactions Between Repotrectinib and Metformin, Digoxin, and Rosuvastatin in Patients With Advanced Solid Tumors
NCT06352528PHASE1COMPLETEDA Study to Assess the Drug Levels of Repotrectinib in Healthy Participants and Participants With Moderate and Severe Hepatic Impairment
NCT06493409PHASE1COMPLETEDA Study to Assess the Effect of Voriconazole and Quinidine on the Pharmacokinetics of a Single Dose of Repotrectinib in Healthy Participants
NCT07223671PHASE1COMPLETEDStudy to Evaluate the Effect of Repotrectinib on the Drug Levels of Transporter and CYP P450 Probe Substrates in Healthy Adult Participants
NCT05926232Not specifiedAVAILABLEExpanded Access for Repotrectinib
NCT07599007Not specifiedNOT_YET_RECRUITINGRepotrectinib Post-Marketing Surveillance in Korean Patients With ROS1-Positive Non-Small Cell Lung Cancer (NSCLC) or Solid Tumors Harboring a Neurotrophic Tyrosine Receptor Kinase (NTRK) Gene Fusion

Clinical evidence (CIViC)

Variant × indication × effect (8 predictive associations from 8 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
ROS1 FusionLung Non-small Cell CarcinomaSensitivity/ResponseRepotrectinibCIViC AEID12021
ROS1 G2032R AND v::ROS1 FusionLung Non-small Cell CarcinomaSensitivity/ResponseRepotrectinibCIViC BEID12022
NTRK3 G623EMammary Analogue Secretory CarcinomaSensitivity/ResponseRepotrectinibCIViC CEID7688
NTRK3 G623R AND EML4::NTRK3 FusionLung Non-small Cell CarcinomaSensitivity/ResponseRepotrectinibCIViC CEID11516
ROS1 G2032RLung Non-small Cell CarcinomaSensitivity/ResponseRepotrectinibCIViC CEID7687
LMNA::NTRK1 FusionCancerSensitivity/ResponseRepotrectinibCIViC DEID11346
LMNA::NTRK1 Fusion AND NTRK1 F589LCancerSensitivity/ResponseRepotrectinibCIViC DEID11348
LMNA::NTRK1 Fusion AND NTRK1 G595RCancerSensitivity/ResponseRepotrectinibCIViC DEID11347

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

151 molecules share ≥1 primary target. Top 60 by shared-target count:

MoleculeSourceStatusShared targets
CRIZOTINIBChEMBL + PubChemPhase 4 (approved)ALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
ENTRECTINIBChEMBL + PubChemPhase 4 (approved)ALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
FEDRATINIBChEMBL + PubChemPhase 4 (approved)ALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
PazopanibChEMBL + PubChemPhase 4 (approved)ALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
RUXOLITINIBChEMBL + PubChemPhase 4 (approved)ALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
LORLATINIBChEMBLPhase 4 (approved)ALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
MIDOSTAURINChEMBLPhase 4 (approved)ALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
NINTEDANIBChEMBLPhase 4 (approved)ALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
LESTAURTINIBChEMBLPhase 3ALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
BMS-754807ChEMBLPhase 2ALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
FORETINIBChEMBLPhase 2ALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
ILORASERTIBChEMBLPhase 2ALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
R-406ChEMBLPhase 2ALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
TOZASERTIBChEMBLPhase 2ALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
AfatinibPubChemApprovedALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
GefitinibPubChemApprovedALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
IdelalisibPubChemApprovedALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
SelumetinibPubChemApprovedALK, JAK2, NTRK1, NTRK2, NTRK3, ROS1
BOSUTINIBChEMBLPhase 4 (approved)ALK, JAK2, NTRK1, NTRK2, NTRK3
CERITINIBChEMBLPhase 4 (approved)ALK, JAK2, NTRK1, NTRK2, ROS1
SUNITINIBChEMBLPhase 4 (approved)ALK, JAK2, NTRK1, NTRK2, NTRK3
DOVITINIBChEMBLPhase 3ALK, JAK2, NTRK1, NTRK2, NTRK3
REBASTINIBChEMBLPhase 2JAK2, NTRK1, NTRK2, NTRK3, ROS1
SELITRECTINIBChEMBLPhase 2ALK, NTRK1, NTRK2, NTRK3, ROS1
SU-014813ChEMBLPhase 2ALK, JAK2, NTRK1, NTRK2, NTRK3
belumosudilPubChemApprovedALK, JAK2, NTRK2, NTRK3, ROS1
QUIZARTINIBChEMBL + PubChemPhase 4 (approved)NTRK1, NTRK2, NTRK3, ROS1
SORAFENIBChEMBL + PubChemPhase 4 (approved)NTRK1, NTRK2, NTRK3, ROS1
INFIGRATINIBChEMBLPhase 4 (approved)ALK, JAK2, NTRK2, ROS1
LAROTRECTINIBChEMBLPhase 4 (approved)NTRK1, NTRK2, NTRK3, ROS1
ALISERTIBChEMBLPhase 3NTRK1, NTRK2, NTRK3, ROS1
DEFACTINIBChEMBLPhase 3JAK2, NTRK1, NTRK2, NTRK3
LINIFANIBChEMBLPhase 3ALK, NTRK1, NTRK2, NTRK3
CENISERTIBChEMBLPhase 2ALK, JAK2, NTRK2, ROS1
ERLOTINIBChEMBL + PubChemPhase 4 (approved)ALK, JAK2, ROS1
AXITINIBChEMBLPhase 4 (approved)JAK2, NTRK1, ROS1
BRIGATINIBChEMBLPhase 4 (approved)ALK, JAK2, ROS1
ENTOSPLETINIBChEMBLPhase 3JAK2, NTRK1, ROS1
ALTIRATINIBChEMBLPhase 2NTRK1, NTRK2, NTRK3
CEP-11981ChEMBLPhase 2ALK, NTRK1, NTRK2
DORAMAPIMODChEMBLPhase 2NTRK1, NTRK2, NTRK3
GZ-389988ChEMBLPhase 2NTRK1, NTRK2, NTRK3
MK-2461ChEMBLPhase 2JAK2, NTRK1, NTRK2
TANDUTINIBChEMBLPhase 2NTRK1, NTRK2, NTRK3
regorafenibPubChemApprovedNTRK1, NTRK2, NTRK3
MomelotinibChEMBL + PubChemPhase 4 (approved)JAK2, ROS1
ALECTINIBChEMBLPhase 4 (approved)ALK, ROS1
GILTERITINIBChEMBLPhase 4 (approved)ALK, ROS1
NILOTINIBChEMBLPhase 4 (approved)NTRK2, NTRK3
PONATINIBChEMBLPhase 4 (approved)JAK2, NTRK1
UPADACITINIBChEMBLPhase 4 (approved)ALK, JAK2
ALVOCIDIBChEMBLPhase 3ALK, JAK2
SITRAVATINIBChEMBLPhase 3NTRK1, NTRK2
AZD-1480ChEMBLPhase 2JAK2, NTRK1
BMS-777607ChEMBLPhase 2NTRK1, NTRK2
DALMELITINIBChEMBLPhase 2JAK2, ROS1
DANUSERTIBChEMBLPhase 2JAK2, NTRK1
LAUROGUADINEChEMBLPhase 2JAK2, NTRK2
OCIFISERTIBChEMBLPhase 2NTRK1, NTRK2
OSI-632ChEMBLPhase 2ALK, ROS1

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

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Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot