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Larotrectinib

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Also known as ARRY-470BAY-2757556BAY2757556Loxo-101LOXO-101 (ARRY-470)LOXO-101LOXO 101LOXO101A-9048VITRAKVIUS8865698, 14Larotrectinib sulfate

Summary

Larotrectinib (CHEMBL3889654) is an approved small molecule (ATC L01EX12) targeting NTRK1; indicated across 4 conditions including neoplasm and plasma cell myeloma; with CIViC clinical evidence for 66 variant-indication associations (e.g. ETV6::NTRK3 Fusion in congenital fibrosarcoma).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01EX12
  • Targets: 1 (NTRK1)
  • Indications: 4 conditions
  • Clinical trials: 12
  • Precision-oncology evidence (CIViC): 66 variant–indication associations
  • Chemistry: 428.4 Da · C21H22F2N6O2

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL3889654
NameLarotrectinib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID46188928
ATCL01EX12
Molecular formulaC21H22F2N6O2
Molecular weight428.4
InChIKeyNYNZQNWKBKUAII-KBXCAEBGSA-N

SMILES: C1C[C@@H](N(C1)C2=NC3=C(C=NN3C=C2)NC(=O)N4CC[C@@H](C4)O)C5=C(C=CC(=C5)F)F

IUPAC name: (3S)-N-[5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide

Also known as: ARRY-470, BAY-2757556, BAY2757556, Larotrectinib, Loxo-101, LOXO-101, LOXO-101 (ARRY-470), LAROTRECTINIB, LOXO-101LOXO 101LOXO101A-9048, VITRAKVI, US8865698, 14, larotrectinib

Parent form; salt/anhydrous children: CHEMBL3989939

Patent coverage: 768 distinct patent families (1,850 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,821 (98%) 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 1Inhibition8.010.1%P04629

Broader ChEMBL bioactivity targets: 6 (assay-derived). Sample: High affinity nerve growth factor receptor, Sphingomyelin phosphodiesterase 3, Activated CDC42 kinase 1, BDNF/NT-3 growth factors receptor, Proto-oncogene tyrosine-protein kinase ROS, NT-3 growth factor receptor.

Bioactivity

ChEMBL activities: 121 potent at pChembl ≥ 5 of 121 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
NTRK39.7IC500.2nMCHEMBL_ACT_25112835
NTRK39.54IC500.29nMCHEMBL_ACT_28811405
NTRK39.54IC500.29nMCHEMBL_ACT_28811414
NTRK39.49IC500.32nMCHEMBL_ACT_28811396
NTRK29.48IC500.33nMCHEMBL_ACT_28811402
NTRK19.4IC500.4nMCHEMBL_ACT_24712367
NTRK29.4IC500.4nMCHEMBL_ACT_28811393
NTRK39.39IC500.41nMCHEMBL_ACT_28811378
NTRK39.36IC500.44nMCHEMBL_ACT_28811369
NTRK39.35IC500.45nMCHEMBL_ACT_28811387
NTRK29.34IC500.46nMCHEMBL_ACT_28811375
NTRK29.34IC500.46nMCHEMBL_ACT_28811384
NTRK29.27IC500.54nMCHEMBL_ACT_28811366
NTRK29.2IC500.63nMCHEMBL_ACT_28811411
NTRK19.14IC500.73nMCHEMBL_ACT_28811399
NTRK19.09IC500.82nMCHEMBL_ACT_28811372
NTRK19.07IC500.86nMCHEMBL_ACT_28811408
NTRK19.05IC500.9nMCHEMBL_ACT_25683792
NTRK19.05IC500.9nMCHEMBL_ACT_26283890
NTRK19.05IC500.9nMCHEMBL_ACT_28811363
NTRK19.02IC500.96nMCHEMBL_ACT_28811381
NTRK29.01IC500.98nMCHEMBL_ACT_25611321
NTRK18.96IC501.1nMCHEMBL_ACT_25989592
NTRK18.95IC501.13nMCHEMBL_ACT_28811390
NTRK18.92IC501.2nMCHEMBL_ACT_22439521
NTRK18.92IC501.2nMCHEMBL_ACT_24365531
NTRK18.92IC501.2nMCHEMBL_ACT_24760037
NTRK18.92IC501.2nMCHEMBL_ACT_24972363
NTRK18.88IC501.31nMCHEMBL_ACT_24843607
NTRK38.77IC501.7nMCHEMBL_ACT_22979696

Target pathways

Aggregated over 1 target gene(s): NTRK1.

Top Reactome pathways

10 total, by targets touching each:

PathwayTargetsGenes
PLC-gamma1 signalling1NTRK1
Signalling to RAS1NTRK1
Frs2-mediated activation1NTRK1
ARMS-mediated activation1NTRK1
Retrograde neurotrophin signalling1NTRK1
NGF-independant TRKA activation1NTRK1
TRKA activation by NGF1NTRK1
Signalling to p38 via RIT and RIN1NTRK1
PI3K/AKT activation1NTRK1
Signalling to STAT31NTRK1

Dominant GO biological processes

GO termTargets
protein phosphorylation1
cell surface receptor protein tyrosine kinase signaling pathway1
spermatogenesis1
axon guidance1
learning or memory1
circadian rhythm1
negative regulation of cell population proliferation1
response to xenobiotic stimulus1
programmed cell death involved in cell development1
positive regulation of neuron projection development1
peptidyl-tyrosine phosphorylation1
olfactory nerve development1
B cell differentiation1
neuron projection development1
response to nutrient levels1

Indications & clinical

Indications

4 indications (1 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
plasma cell myeloma2MONDO:0009693EFO:0001378
thyroid gland carcinoma2MONDO:0015075EFO:0002892
diffuse intrinsic pontine glioma0MONDO:0006033EFO:1000026

Clinical trials

Total trials: 12.

Phase distribution

PhaseTrials
PHASE210
PHASE41
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT07010393PHASE4NOT_YET_RECRUITINGGenotype-Driven Neoadjuvant Therapy for Locally Advanced Thyroid Cancer: A Real-World Cohort Study
NCT02465060PHASE2ACTIVE_NOT_RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
NCT03155620PHASE2ACTIVE_NOT_RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03213704PHASE2ACTIVE_NOT_RECRUITINGLarotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03834961PHASE2ACTIVE_NOT_RECRUITINGLarotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia
NCT04879121PHASE2RECRUITINGLarotrectinib for the Treatment of NTRK Amplification Positive, Locally Advanced or Metastatic Solid Tumors
NCT05725200PHASE2RECRUITINGStudy to Investigate Outcome of Individualized Treatment in Patients With Metastatic Colorectal Cancer
NCT05783323PHASE2RECRUITINGLarotrectinib to Enhance RAI Avidity in Differentiated Thyroid Cancer
NCT06390852PHASE2ACTIVE_NOT_RECRUITINGTesting LOXO-101 as Potentially Targeted Treatment in Cancers With NTRK Genetic Changes (MATCH - Subprotocol Z1E)
NCT06482086PHASE2RECRUITINGEfficacy of Organoid-Based Drug Screening to Guide Treatment for Locally Advanced Thyroid Cancer
NCT06563999PHASE2RECRUITINGNeoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations.
NCT04655404EARLY_PHASE1RECRUITINGA Pilot Study of Larotrectinib for Newly-Diagnosed High-Grade Glioma With NTRK Fusion

Clinical evidence (CIViC)

Variant × indication × effect (66 predictive associations from 75 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
ETV6::NTRK3 FusionCongenital FibrosarcomaSensitivity/ResponseLarotrectinibCIViC AEID6099 +3
ETV6::NTRK3 FusionSolid TumorSensitivity/ResponseLarotrectinibCIViC AEID7496
NTRK1 FusionSolid TumorSensitivity/ResponseLarotrectinibCIViC AEID6567
NTRK2 FusionSolid TumorSensitivity/ResponseLarotrectinibCIViC AEID10392
NTRK3 FusionSolid TumorSensitivity/ResponseLarotrectinibCIViC AEID6568
NTRK1 Fusion AND NTRK1 F589LSolid TumorResistanceLarotrectinibCIViC AEID11542
NTRK1 Fusion AND NTRK1 G595RSolid TumorResistanceLarotrectinibCIViC AEID11540
NTRK1 Fusion AND NTRK1 G667SSolid TumorResistanceLarotrectinibCIViC AEID11543
NTRK3 F617LSolid TumorResistanceLarotrectinibCIViC AEID11571
NTRK3 Fusion AND NTRK3 G623RSolid TumorResistanceLarotrectinibCIViC AEID11541
NTRK3 Fusion AND NTRK3 G696ASolid TumorResistanceLarotrectinibCIViC AEID11544
NTRK1 FusionSarcomaSensitivity/ResponseLarotrectinibCIViC BEID6569
NTRK3 FusionCancerSensitivity/ResponseLarotrectinibCIViC BEID2954
NTRK1 G595RSolid TumorResistanceLarotrectinibCIViC BEID7267
ETV6::NTRK3 FusionB-lymphoblastic Leukemia/lymphomaSensitivity/ResponseLarotrectinibCIViC CEID7993 +2
LMNA::NTRK1 FusionSarcomaSensitivity/ResponseLarotrectinibCIViC CEID2955 +1
NTRK1 FusionPancreatic CancerSensitivity/ResponseLarotrectinibCIViC CEID6051 +1
PDE4DIP::NTRK1 FusionSarcomaSensitivity/ResponseLarotrectinibCIViC CEID6102 +1
SQSTM1::NTRK1 FusionCongenital FibrosarcomaSensitivity/ResponseLarotrectinibCIViC CEID6103 +1
EML4::NTRK3 FusionHigh Grade GliomaSensitivity/ResponseLarotrectinibCIViC CEID11100
ETV6::NTRK2 FusionAcute Myeloid LeukemiaSensitivity/ResponseLarotrectinibCIViC CEID6396
ETV6::NTRK2 Fusion AND TERT c.-124C.TPapillary Thyroid CarcinomaSensitivity/ResponseLarotrectinibCIViC CEID11278
ETV6::NTRK3 FusionCongenital Mesoblastic NephromaSensitivity/ResponseLarotrectinibCIViC CEID10840
ETV6::NTRK3 FusionHigh Grade GliomaSensitivity/ResponseLarotrectinibCIViC CEID10931
ETV6::NTRK3 FusionHematologic CancerSensitivity/ResponseLarotrectinibCIViC CEID6395
ETV6::NTRK3 FusionBreast Secretory CarcinomaSensitivity/ResponseLarotrectinibCIViC CEID6475
ETV6::NTRK3 FusionB-lymphoblastic Leukemia/lymphomaSensitivity/ResponseEtoposide + Methotrexate + LarotrectinibCIViC CEID8917
KANK1::NTRK2 FusionAnaplastic EpendymomaSensitivity/ResponseLarotrectinibCIViC CEID10360
KANK1::NTRK2 FusionGlioblastomaSensitivity/ResponseLarotrectinibCIViC CEID10361
LMNA::NTRK1 FusionSolid TumorSensitivity/ResponseLarotrectinibCIViC CEID9588

+36 more predictive associations (showing top 30 by level).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

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

MoleculeSourceStatusShared targets
CRIZOTINIBChEMBL + PubChemPhase 4 (approved)NTRK1
REPOTRECTINIBChEMBL + PubChemPhase 4 (approved)NTRK1
ABEMACICLIBChEMBLPhase 4 (approved)NTRK1
AMITRIPTYLINEChEMBLPhase 4 (approved)NTRK1
AXITINIBChEMBLPhase 4 (approved)NTRK1
BOSUTINIBChEMBLPhase 4 (approved)NTRK1
CABOZANTINIBChEMBLPhase 4 (approved)NTRK1
CERITINIBChEMBLPhase 4 (approved)NTRK1
ENTRECTINIBChEMBLPhase 4 (approved)NTRK1
FEDRATINIBChEMBLPhase 4 (approved)NTRK1
LORLATINIBChEMBLPhase 4 (approved)NTRK1
MIDOSTAURINChEMBLPhase 4 (approved)NTRK1
NINTEDANIBChEMBLPhase 4 (approved)NTRK1
PONATINIBChEMBLPhase 4 (approved)NTRK1
QUIZARTINIBChEMBLPhase 4 (approved)NTRK1
RUXOLITINIBChEMBLPhase 4 (approved)NTRK1
SORAFENIBChEMBLPhase 4 (approved)NTRK1
SUNITINIBChEMBLPhase 4 (approved)NTRK1
ALISERTIBChEMBLPhase 3NTRK1
CRENOLANIBChEMBLPhase 3NTRK1
DEFACTINIBChEMBLPhase 3NTRK1
DOVITINIBChEMBLPhase 3NTRK1
ENTOSPLETINIBChEMBLPhase 3NTRK1
LESTAURTINIBChEMBLPhase 3NTRK1
LINIFANIBChEMBLPhase 3NTRK1
SITRAVATINIBChEMBLPhase 3NTRK1
ALTIRATINIBChEMBLPhase 2NTRK1
AZD-1480ChEMBLPhase 2NTRK1
BMS-754807ChEMBLPhase 2NTRK1
BMS-777607ChEMBLPhase 2NTRK1
CEP-11981ChEMBLPhase 2NTRK1
DANUSERTIBChEMBLPhase 2NTRK1
DORAMAPIMODChEMBLPhase 2NTRK1
ENMD-2076ChEMBLPhase 2NTRK1
FORETINIBChEMBLPhase 2NTRK1
GOLVATINIBChEMBLPhase 2NTRK1
GZ-389988ChEMBLPhase 2NTRK1
ILORASERTIBChEMBLPhase 2NTRK1
MERESTINIBChEMBLPhase 2NTRK1
MILCICLIBChEMBLPhase 2NTRK1
MK-2461ChEMBLPhase 2NTRK1
OCIFISERTIBChEMBLPhase 2NTRK1
PEXMETINIBChEMBLPhase 2NTRK1
PICTILISIBChEMBLPhase 2NTRK1
R-406ChEMBLPhase 2NTRK1
REBASTINIBChEMBLPhase 2NTRK1
SELITRECTINIBChEMBLPhase 2NTRK1
SU-014813ChEMBLPhase 2NTRK1
TANDUTINIBChEMBLPhase 2NTRK1
TOZASERTIBChEMBLPhase 2NTRK1
UCN-01ChEMBLPhase 2NTRK1
AfatinibPubChemApprovedNTRK1
BinimetinibPubChemApprovedNTRK1
dacomitinibPubChemApprovedNTRK1
FostamatinibPubChemApprovedNTRK1
GefitinibPubChemApprovedNTRK1
IdelalisibPubChemApprovedNTRK1
PazopanibPubChemApprovedNTRK1
regorafenibPubChemApprovedNTRK1
SelumetinibPubChemApprovedNTRK1

About this page

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

Generated
Atlas version
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Sources 29

This page pulls from 29 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot