larotrectinib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5305 1223403-58-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • larotrectinib
  • vitrakvi
  • LOXO-101
  • ARRY-470
Larotrectinib is an inhibitor of the tropomyosin receptor kinases (TRK), TRKA, TRKB, and TRKC. In a broad panel of purified enzyme assays, larotrectinib inhibited TRKA, TRKB, and TRKC with IC50 values between 5-11 nM. One other kinase TNK2 was inhibited at approximately 100-fold higher concentration. TRKA, B, and C are encoded by the genes NTRK1, NTRK2, and NTRK3.Chromosomal rearrangements involving in-frame fusions of these genes with various partners can result in constitutively-activated chimeric TRK fusion proteins that can act as an oncogenic driver, promoting cell proliferation and survival in tumor cell lines.
  • Molecular weight: 428.44
  • Formula: C21H22F2N6O2
  • CLOGP: 2
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 2
  • TPSA: 86
  • ALOGS: -3.26
  • ROTB: 3

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Sept. 19, 2019 EMA Bayer AG
Nov. 26, 2018 FDA LOXO ONCOLOGY INC

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EX12 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Other protein kinase inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000193859 Tropomyosin Receptor Kinases Inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Malignant Neoplasm indication 367651003

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.36 acidic
pKa2 3.52 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 25MG BASE VITRAKVI BAYER HLTHCARE N210861 Nov. 26, 2018 RX CAPSULE ORAL Nov. 26, 2023 NEW CHEMICAL ENTITY
EQ 25MG BASE VITRAKVI BAYER HLTHCARE N210861 Nov. 26, 2018 RX CAPSULE ORAL Nov. 26, 2025 INDICATED FOR THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS WITH SOLID TUMORS THAT ARE METASTATIC OR WHERE SURGICAL RESECTION IS LIKELY TO RESULT IN SEVERE MORBIDITY
EQ 25MG BASE VITRAKVI BAYER HLTHCARE N210861 Nov. 26, 2018 RX CAPSULE ORAL Nov. 26, 2025 INDICATED FOR THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS WITH SOLID TUMORS THAT HAVE A NEUROTROPHIC RECEPTOR TYROSINE KINULLSE (NTRK) GENE FUSION WITHOUT A KNOWN ACQUIRED RESISTANCE MUTATION
EQ 25MG BASE VITRAKVI BAYER HLTHCARE N210861 Nov. 26, 2018 RX CAPSULE ORAL Nov. 26, 2025 INDICATED FOR THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS WITH SOLID TUMORS THAT HAVE NO SATISFACTORY ALTERNULLTIVE TREATMENTS OR THAT HAVE PROGRESSED FOLLOWING TREATMENT

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
High affinity nerve growth factor receptor Kinase INHIBITOR IC50 8.19 SCIENTIFIC LITERATURE DRUG LABEL
BDNF/NT-3 growth factors receptor Kinase INHIBITOR IC50 8.09 SCIENTIFIC LITERATURE DRUG LABEL
NT-3 growth factor receptor Kinase INHIBITOR IC50 7.97 SCIENTIFIC LITERATURE DRUG LABEL

External reference:

IDSource
4038034 VANDF
C4278057 UMLSCUI
CHEMBL3889654 ChEMBL_ID
CHEMBL3989939 ChEMBL_ID
D11137 KEGG_DRUG
46188928 PUBCHEM_CID
DB14723 DRUGBANK_ID
C000609083 MESH_SUPPLEMENTAL_RECORD_UI
8909 IUPHAR_LIGAND_ID
10360 INN_ID
PF9462I9HX UNII
2105628 RXNORM
299174 MMSL
d09074 MMSL
017848 NDDF
782977003 SNOMEDCT_US
782991009 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
VITRAKVI HUMAN PRESCRIPTION DRUG LABEL 1 50419-390 CAPSULE 25 mg ORAL NDA 28 sections
VITRAKVI HUMAN PRESCRIPTION DRUG LABEL 1 50419-391 CAPSULE 100 mg ORAL NDA 28 sections
VITRAKVI HUMAN PRESCRIPTION DRUG LABEL 1 50419-392 SOLUTION, CONCENTRATE 20 mg OROPHARYNGEAL NDA 28 sections
VITRAKVI HUMAN PRESCRIPTION DRUG LABEL 1 71777-390 CAPSULE 25 mg ORAL NDA 27 sections
VITRAKVI HUMAN PRESCRIPTION DRUG LABEL 1 71777-391 CAPSULE 100 mg ORAL NDA 27 sections
VITRAKVI HUMAN PRESCRIPTION DRUG LABEL 1 71777-392 SOLUTION 20 mg ORAL NDA 27 sections