repotrectinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5751 1802220-02-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • repotrectinib
  • TRX-0005
  • augtyro
Repotrectinib is an inhibitor of proto-oncogene tyrosine-protein kinase ROS1 (ROS1) and of the tropomyosin receptor tyrosine kinases (TRKs) TRKA, TRKB, and TRKC. Fusion proteins that include ROS1 domains can drive tumorigenic potential through hyperactivation of downstream signaling pathways leading to unconstrained cell proliferation. Repotrectinib exhibited anti-tumor activity in cultured cells expressing ROS1 fusions and mutations including SDC4-ROS1, SDC4-ROS1 G2032R, CD74-ROS1, CD74-ROS1 G2032R, CD74- ROS1 D2033N, and CD74-ROS1 L2026M.
  • Molecular weight: 355.37
  • Formula: C18H18FN5O2
  • CLOGP: 2.55
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 2
  • TPSA: 80.55
  • ALOGS:
  • ROTB: 0
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.866 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 10.423 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 40.365 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 3.214 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 10.800 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 24.030 % High 1
herg hERG pIC50 4.481 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 2.911 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 36.898 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 8.320 % High 1
kinase-safety-class AAK1,ABL1,ABL2,ACVR2A,ACVR2B,ACVRL1,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,CAMK2A,CAMK2B,CAMK2D,CAMK2G,CDK1,CDK14,CDK16,CDK19,CDK2,CDK3,CDK4,CDK6,CDK7,CDK8,CDK9,CHEK1,CLK1,CLK2,CLK4,CSF1R,DDR1,DYRK1A,DYRK1B,DYRK2,DYRK3,EGFR,EIF2AK3,EPHB1,EPHB4,ERBB2,FGFR1,FLT3,FLT4,FYN,GAK,GRK2,GSK3A,GSK3B,HASPIN,HIPK2,INSR,IRAK1,IRAK3,IRAK4,ITK,JAK1,JAK2,JAK3,KDR,KIT,LCK,LRRK2,LYN,MAP2K1,MAP3K1,MAP3K10,MAP3K11,MAP3K14,MAP3K19,MAP3K2,MAP3K21,MAP3K3,MAP3K7,MAP3K9,MAP4K1,MAP4K2,MAP4K3,MAP4K4,MAP4K5,MAPK1,MAPK10,MAPK15,MAPK3,MAPK7,MARK1,MARK2,MARK3,MARK4,MELK,MET,MINK1,MKNK1,MKNK2,MST1R,NTRK1,NTRK2,NTRK3,NUAK1,PAK4,PDGFRB,PDK1,PDK2,PDK4,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PIM3,PLK4,PRKAA1,PRKAA2,PRKCD,PRKCZ,PRKDC,RET,RIPK3,ROCK1,ROCK2,RPS6KA1,SIK2,SIK3,SRC,STK10,STK17A,STK33,STK4,SYK,TBK1,TEK,TGFBR1,TNIK,TNK1,TTK,TYRO3,UHMK1,ULK1,ULK2,YES1 142
kinase-selectivity-class AAK1,ABL2,ACVR2A,ACVR2B,ACVRL1,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,BTK,CAMK2A,CAMK2B,CAMK2D,CDK1,CDK16,CDK2,CDK3,CDK6,CDK7,CDK8,CDK9,CHUK,CLK2,CLK4,CSF1R,CSNK2A2,DDR1,DYRK1A,DYRK1B,DYRK2,DYRK3,EGFR,EPHB3,EPHB4,ERBB2,FGFR1,FLT1,FLT3,FLT4,FYN,GAK,GRK2,GSK3A,GSK3B,HASPIN,HIPK2,IGF1R,INSR,IRAK1,IRAK3,IRAK4,JAK1,JAK2,JAK3,KDR,KIT,LCK,LRRK2,LYN,MAP2K1,MAP2K3,MAP3K1,MAP3K10,MAP3K11,MAP3K14,MAP3K2,MAP3K21,MAP3K7,MAP3K9,MAP4K1,MAP4K3,MAP4K5,MAPK1,MARK1,MARK2,MARK3,MARK4,MELK,MET,MINK1,MKNK1,MKNK2,MST1R,NTRK1,NTRK3,NUAK1,PAK4,PDGFRB,PDK1,PIK3CA,PIK3CD,PIM3,PRKAA1,PRKAA2,PRKCD,PRKDC,PTK2,RET,RIPK1,RIPK3,ROCK1,SGK1,SIK2,SIK3,SRC,STK10,STK11,STK17A,STK33,STK4,SYK,TEK,TGFBR1,TNIK,TNK1,TYRO3,UHMK1,ULK1,ULK2,YES1 124
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 36.983 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 35.156 High 1
mh-clint Mouse hepatocyte intrinsic clearance 13.213 High 1
mppb Mouse plasma protein binding (% unbound) 10.800 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 58.749 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 19.310 % High 1
rat-kpuu-brain Rat brain Kpuu 0.012 % High 1
rh-clint Rat hepatocyte intrinsic clearance 13.490 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 63.420 % High 1
rppb Rat plasma protein binding (% unbound) 9.150 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 43.451 uM High 1

Approvals:

DateAgencyCompanyOrphan
Nov. 15, 2023 FDA BRISTOL

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

None

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EX28 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Other protein kinase inhibitors
MeSH PA D000092004 Tyrosine Kinase Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000185506 Cytochrome P450 3A4 Inducers
FDA MoA N0000194093 Proto-Oncogene Tyrosine-Protein Kinase ROS1 Inhibitors
FDA MoA N0000194094 Tropomyosin Receptor Tyrosine Kinase A Inhibitors
FDA MoA N0000194095 Tropomyosin Receptor Tyrosine Kinase B Inhibitors
FDA MoA N0000194096 Tropomyosin Receptor Tyrosine Kinase C Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:62434 EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor

Related Drugs by ATC class:

L01EX Other protein kinase inhibitors 21 drugs
avapritinibcabozantinibcapivasertibentrectinibgilteritiniblarotrectiniblenvatinibmidostaurinnintedanibpazopanibpexidartinibpralsetinib show all 21 →

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Reactive oxygen species 1 positive non-small cell lung cancer indication 72242500




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
160MG AUGTYRO BRISTOL N218213 June 11, 2024 RX CAPSULE ORAL 12310968 July 20, 2036 TREATMENT OF ADULT PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ROS1-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC)
40MG AUGTYRO BRISTOL N218213 Nov. 15, 2023 RX CAPSULE ORAL 12310968 July 20, 2036 TREATMENT OF ADULT PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ROS1-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC)
160MG AUGTYRO BRISTOL N218213 June 11, 2024 RX CAPSULE ORAL 11452725 July 24, 2036 TREATMENT OF ADULT AND PEDIATRIC PATIENTS >12 YEARS WITH SOLID TUMORS AND NTRK GENE FUSION THAT ARE LOCALLY ADVANCED OR METASTATIC OR LIKELY SURGICALLY UNRESECTABLE, AND HAVE PROGRESSED FOLLOWING TREATMENT OR HAVE NO SATISFACTORY ALTERNATIVE THERAPY
160MG AUGTYRO BRISTOL N218213 June 11, 2024 RX CAPSULE ORAL 11452725 July 24, 2036 TREATMENT OF ADULT PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ROS1-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC)
40MG AUGTYRO BRISTOL N218213 Nov. 15, 2023 RX CAPSULE ORAL 11452725 July 24, 2036 TREATMENT OF ADULT AND PEDIATRIC PATIENTS >12 YEARS WITH SOLID TUMORS AND NTRK GENE FUSION THAT ARE LOCALLY ADVANCED OR METASTATIC OR LIKELY SURGICALLY UNRESECTABLE, AND HAVE PROGRESSED FOLLOWING TREATMENT OR HAVE NO SATISFACTORY ALTERNATIVE THERAPY
40MG AUGTYRO BRISTOL N218213 Nov. 15, 2023 RX CAPSULE ORAL 11452725 July 24, 2036 TREATMENT OF ADULT PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ROS1-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC)

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
160MG AUGTYRO BRISTOL N218213 June 11, 2024 RX CAPSULE ORAL Nov. 15, 2028 NEW CHEMICAL ENTITY
40MG AUGTYRO BRISTOL N218213 Nov. 15, 2023 RX CAPSULE ORAL Nov. 15, 2028 NEW CHEMICAL ENTITY
160MG AUGTYRO BRISTOL N218213 June 11, 2024 RX CAPSULE ORAL Nov. 15, 2030 FDA HAS NOT RECOGNIZED ORPHAN-DRUG EXCLUSIVITY (ODE) FOR THIS DRUG, BUT IT CONTAINS THE SAME ACTIVE MOIETY OR MOIETIES AS ANOTHER DRUG(S) THAT WAS ELIGIBLE FOR ODE, AND ALSO SHARES ODE-PROTECTED USE(S) OR INDICATION(S) WITH THAT DRUG(S). AN APPLICATION SEEKING APPROVAL FOR THE SAME ACTIVE MOIETY OR MOIETIES, INCLUDING AN ANDA THAT CITES THIS NDA AS ITS BASIS OF SUBMISSION, MAY NOT BE APPROVED FOR SUCH ODE-PROTECTED USE(S) AND INDICATION(S)
40MG AUGTYRO BRISTOL N218213 Nov. 15, 2023 RX CAPSULE ORAL Nov. 15, 2030 TREATMENT OF ADULT PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ROS1-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC) WITH ADENOCARCINOMA HISTOLOGY
160MG AUGTYRO BRISTOL N218213 June 11, 2024 RX CAPSULE ORAL June 13, 2031 TREATMENT OF ADULT AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER WITH SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION, ARE LOCALLY ADVANCED OR METASTATIC OR WHERE SURGICAL RESECTION IS LIKELY TO RESULT IN SEVERE MORBIDITY, AND HAVE PROGRESSED FOLLOWING TREATMENT OR HAVE NO SATISFACTORY ALTERNATIVE THERAPY
40MG AUGTYRO BRISTOL N218213 Nov. 15, 2023 RX CAPSULE ORAL June 13, 2031 TREATMENT OF ADULT AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER WITH SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION, ARE LOCALLY ADVANCED OR METASTATIC OR WHERE SURGICAL RESECTION IS LIKELY TO RESULT IN SEVERE MORBIDITY, AND HAVE PROGRESSED FOLLOWING TREATMENT OR HAVE NO SATISFACTORY ALTERNATIVE THERAPY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
High affinity nerve growth factor receptor Kinase INHIBITOR IC50 9.27 SCIENTIFIC LITERATURE DRUG LABEL
BDNF/NT-3 growth factors receptor Kinase INHIBITOR IC50 9.53 SCIENTIFIC LITERATURE DRUG LABEL
NT-3 growth factor receptor Kinase INHIBITOR IC50 9.68 SCIENTIFIC LITERATURE DRUG LABEL
Proto-oncogene tyrosine-protein kinase ROS Kinase INHIBITOR IC50 10.15 SCIENTIFIC LITERATURE DRUG LABEL
Tyrosine-protein kinase Lck Kinase INHIBITOR IC50 7.73 SCIENTIFIC LITERATURE
Tyrosine-protein kinase Yes Kinase INHIBITOR IC50 8.67 SCIENTIFIC LITERATURE
Focal adhesion kinase 1 Kinase INHIBITOR IC50 8.16 SCIENTIFIC LITERATURE
Tyrosine-protein kinase JAK1 Kinase INHIBITOR IC50 7.72 SCIENTIFIC LITERATURE
Tyrosine-protein kinase JAK2 Kinase INHIBITOR IC50 8.98 SCIENTIFIC LITERATURE
Ephrin type-A receptor 8 Kinase INHIBITOR IC50 7.30 SCIENTIFIC LITERATURE
Tyrosine-protein kinase Lyn Kinase INHIBITOR IC50 8.78 SCIENTIFIC LITERATURE
Tyrosine-protein kinase Fgr Kinase INHIBITOR IC50 8.52 SCIENTIFIC LITERATURE
ALK tyrosine kinase receptor Kinase INHIBITOR IC50 8.98 SCIENTIFIC LITERATURE
Tyrosine-protein kinase Fyn Kinase INHIBITOR IC50 8.98 SCIENTIFIC LITERATURE
Epithelial discoidin domain-containing receptor 1 Kinase INHIBITOR IC50 8.24 SCIENTIFIC LITERATURE
Tyrosine-protein kinase BTK Kinase INHIBITOR IC50 7.63 SCIENTIFIC LITERATURE
Tyrosine-protein kinase receptor UFO Kinase INHIBITOR IC50 6.83 SCIENTIFIC LITERATURE
Non-receptor tyrosine-protein kinase TYK2 Kinase INHIBITOR IC50 7.67 SCIENTIFIC LITERATURE
Tyrosine-protein kinase TXK Kinase INHIBITOR IC50 8.50 SCIENTIFIC LITERATURE
Discoidin domain-containing receptor 2 Kinase INHIBITOR IC50 7.64 SCIENTIFIC LITERATURE
Leukocyte tyrosine kinase receptor Kinase INHIBITOR IC50 7.66 SCIENTIFIC LITERATURE
NUAK family SNF1-like kinase 1 Kinase INHIBITOR IC50 8.35 SCIENTIFIC LITERATURE
Ephrin type-A receptor 1 Kinase INHIBITOR IC50 7.60 SCIENTIFIC LITERATURE
MAP/microtubule affinity-regulating kinase 3 Kinase INHIBITOR IC50 6.29 SCIENTIFIC LITERATURE
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase INHIBITOR IC50 7.33 SCIENTIFIC LITERATURE
Tyrosine-protein kinase JAK3 Kinase INHIBITOR IC50 7.30 SCIENTIFIC LITERATURE
Proto-oncogene tyrosine-protein kinase Src Kinase INHIBITOR IC50 8.28 SCIENTIFIC LITERATURE

External reference:

IDSource
CHEBI:229220 CHEBI
7GI PDB_CHEM_ID
CHEMBL4298138 ChEMBL_ID
C000708510 MESH_SUPPLEMENTAL_RECORD_UI
10316 IUPHAR_LIGAND_ID
DB16826 DRUGBANK_ID
933536591000036100 SNOMEDCT_US
4042793 VANDF
C4524909 UMLSCUI
10931 INN_ID
135565923 PUBCHEM_CID
374347 MMSL
42179 MMSL
d10133 MMSL
019609 NDDF
08O3FQ4UNP UNII
2670644 RXNORM
D11454 KEGG_DRUG
08O3FQ4UNP INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Augtyro HUMAN PRESCRIPTION DRUG LABEL 1 0003-4040 CAPSULE 40 mg ORAL NDA 29 sections
Augtyro HUMAN PRESCRIPTION DRUG LABEL 1 0003-4160 CAPSULE 160 mg ORAL NDA 29 sections