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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H22F2N6O2
Molecular Weight 428.4352
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LAROTRECTINIB

SMILES

O[C@H]1CCN(C1)C(=O)NC2=C3N=C(C=CN3N=C2)N4CCC[C@@H]4C5=C(F)C=CC(F)=C5

InChI

InChIKey=NYNZQNWKBKUAII-KBXCAEBGSA-N
InChI=1S/C21H22F2N6O2/c22-13-3-4-16(23)15(10-13)18-2-1-7-28(18)19-6-9-29-20(26-19)17(11-24-29)25-21(31)27-8-5-14(30)12-27/h3-4,6,9-11,14,18,30H,1-2,5,7-8,12H2,(H,25,31)/t14-,18+/m0/s1

HIDE SMILES / InChI
Molecular Formula C21H22F2N6O2
Molecular Weight 428.4352
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Approval Year

Unknown
86413
Substance Class Chemical
Created
by admin
on Sat Dec 16 09:51:56 UTC 2023
Edited
by admin
on Sat Dec 16 09:51:56 UTC 2023
Record UNII
PF9462I9HX
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LAROTRECTINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
BAY-2757556
Code English
LOXO-101
Code English
ARRY-470
Code English
LAROTRECTINIB [USAN]
Common Name English
1-PYRROLIDINECARBOXAMIDE, N-(5-((2R)-2-(2,5-DIFLUOROPHENYL)-1-PYRROLIDINYL)PYRAZOLO(1,5-A)PYRIMIDIN-3-YL)-3-HYDROXY-, (3S)-
Systematic Name English
larotrectinib [INN]
Common Name English
Larotrectinib [WHO-DD]
Common Name English
(3S)-N-(5-((2R)-2-(2,5-DIFLUOROPHENYL)PYRROLIDIN- 1-YL)PYRAZOLO(1,5-A)PYRIMIDIN-3-YL)-3-HYDROXYPYRROLIDINE- 1-CARBOXAMIDE
Systematic Name English
LAROTRECTINIB [MI]
Common Name English
BAY2757556
Code English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
FDA ORPHAN DRUG 578317
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
NCI_THESAURUS C1967
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
EU-Orphan Drug EU/3/18/2098
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
Code System Code Type Description
DRUG BANK
DB14723
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY
CAS
1223403-58-4
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY
MANUFACTURER PRODUCT INFORMATION
LOXO-101
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY MedKoo CAT NO: 206207CAS NO: 1223403-58-4Description: LOXO-101, also known as ARRY-470, is an orally bioavailable, potent, ATP-competitive inhibitor of TRKA, TRKB, and TRKC. LOXO-101 has IC50 values in the low nanomolar range for inhibition of all three TRK family members in binding and cellular assays, with 100x selectivity over other kinases, and has shown acceptable pharmaceutical properties and safety in nonclinical models. The TRK family of neurotrophin receptors, TRKA, TRKB, and TRKC (encoded by NTRK1, NTRK2, and NTRK3 genes, respectively) and their neurotrophin ligands regulate growth, differentiation and survival of neurons. (Last updated: 6/9/2016).
DRUG CENTRAL
5305
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY
EPA CompTox
DTXSID101020707
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY
NCI_THESAURUS
C115977
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY
FDA UNII
PF9462I9HX
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY
ChEMBL
CHEMBL3545075
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY
MERCK INDEX
m12207
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY
PUBCHEM
46188928
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY
SMS_ID
100000174559
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY
RXCUI
2105628
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY
DAILYMED
PF9462I9HX
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY
USAN
DE-156
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY
MANUFACTURER PRODUCT INFORMATION
ARRY 470
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY Biological Activity: LOXO-101 is an orally bioavailable, potent, ATP-competitive inhibitor of TRKA, TRKB, and TRKC. LOXO-101 has IC50 values in the low nanomolar range for inhibition of all three TRK family members in binding and cellular assays, with 100x selectivity over other kinases, and has shown acceptable pharmaceutical properties and safety in nonclinical models. The TRK family of neurotrophin receptors, TRKA, TRKB, and TRKC (encoded by NTRK1, NTRK2, and NTRK3 genes, respectively) and their neurotrophin ligands regulate growth, differentiation and survival of neurons. Translocations involving the TRK kinase domain, mutations involving the TRK ligand-binding site, amplifications of NTRK, TRK splice variants, and autocrine/paracrine signaling are described in diverse tumor types, and may contribute to tumorigenesis. LOXO-101 is currently being developed by Loxo Oncology, Inc.
INN
10360
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY
WIKIPEDIA
Larotrectinib
Created by admin on Sat Dec 16 09:51:57 UTC 2023 , Edited by admin on Sat Dec 16 09:51:57 UTC 2023
PRIMARY
Related Record Type Details
CYTOCHROME P450 3A4
METABOLIC ENZYME -> INDUCER
Structure of LAROTRECTINIB
EXCRETED UNCHANGED
mediated primarily by oxidative N-dealkylation with the subsequent cleavage of the 3-hydroxypyrrolidine carboxamide moiety and formation of the secondary glucuronide M14, the most abundant circulating and excreted metabolite.
FECAL
Structure of Larotrectinib hydrochloride
SALT/SOLVATE -> PARENT
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> SUBSTRATE
In overexpressing BCRP and P-gp cell line, the estimate Km for both transporters is >300 μM.
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> SUBSTRATE
In overexpressing BCRP and P-gp cell line, the estimate Km for both transporters is >300 μM. Coadministration of larotrectinib with a single dose of a P-gp inhibitor (rifampin), increased the AUCinf of larotrectinib by 1.7-fold and the Cmax by 1.8-fold as compared to larotrectinib administered alone.
HIGH AFFINITY NERVE GROWTH FACTOR RECEPTOR
TARGET -> INHIBITOR
Active against NTRK gene fusions. Competitive to ATP binding site.
COMPETITIVE INHIBITOR
IC50
Structure of LAROTRECTINIB
EXCRETED UNCHANGED
Following oral administration of a single [14C] radiolabeled 100 mg dose of larotrectinib to healthy subjects, 58% (5% unchanged) of the administered radioactivity was recovered in feces and 39% (20% unchanged) was recovered in urine
URINE
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
Drug interactions with Cyp3A4 inhibitors. Up to a 4.3 fold increase.
MAJOR
Structure of LAROTRECTINIB SULFATE
SALT/SOLVATE -> PARENT
NT-3 GROWTH FACTOR RECEPTOR
TARGET -> INHIBITOR
IC50
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
CYTOCHROME P450 3A4
METABOLIC ENZYME -> INHIBITOR
Coadministration of multiple doses of larotrectinib with a sensitive CYP3A4 substrate (midazolam) increased the AUCinf and Cmax of midazolam by 1.7-fold as compared to midazolam administered alone.
BDNF/NT-3 GROWTH FACTORS RECEPTOR
TARGET -> INHIBITOR
IC50
Related Record Type Details
Structure of LAROTRECTINIB
ACTIVE MOIETY
LOXO-101 has IC50 values in the low nanomolar range for inhibition of all three TRK family members in binding and cellular assays, with 100x selectivity over other kinases, and has shown acceptable pharmaceutical properties and safety in preclinical models. LOXO-101 is an orally bioavailable, potent, ATP-competitive inhibitor of TRKA, TRKB, and TRKC. LOXO-101 has IC50 values in the low nanomolar range for inhibition of all three TRK family members in binding and cellular assays, with 100x selectivity over other kinases, and has shown acceptable pharmaceutical properties and safety in nonclinical models.
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC ORAL

DOSE

Volume of Distribution PHARMACOKINETIC DOSE

Tmax PHARMACOKINETIC BID

NIH
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