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
SMILES
O[C@H]1CCN(C1)C(=O)NC2=C3N=C(C=CN3N=C2)N4CCC[C@@H]4C5=CC(F)=CC=C5F
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
| Molecular Formula | C21H22F2N6O2 |
| Molecular Weight | 428.4352 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Larotrectinib (previously known as ARRY-470 and LOXO-101) is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Larotrectinib is in phase II clinical trials for the treatment patients with solid tumors, non-Hodgkin lymphoma and for the pediatric patients with advanced solid or primary CNS tumors.
CNS Activity
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. | 2013 Nov |
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| An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101. | 2015 Oct |
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| Targeting NTRK fusion in non-small cell lung cancer: rationale and clinical evidence. | 2017 Jun |
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| Rapid Response to Larotrectinib (LOXO-101) in an Adult Chemotherapy-Naive Patients With Advanced Triple-Negative Secretory Breast Cancer Expressing ETV6-NTRK3 Fusion. | 2018 Jun |
Sample Use Guides
Oral capsule of LOXO-101 (ARRY-470 (FREE BASE)) - 100mg BID
Route of Administration:
Oral
ARRY-470 is a selective kinase inhibitor with nanomolar activity against TRKA/B/C but no other significant kinase inhibition below 1000nM. Treatment of cells expressing MPRIP- or CD74-NTRK1 with ARRY-470, CEP-701 and, to a lesser extent, crizotinib, inhibited autophosphorylation of RIP-TRKA and CD74-TRKA. It induces cell-cycle arrest in G1 and apoptosis of KM12 cells.
| Substance Class |
Chemical
Created
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Tue Mar 06 11:02:27 UTC 2018
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Tue Mar 06 11:02:27 UTC 2018
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| Record UNII |
PF9462I9HX
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Validated (UNII)
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1223403-58-4
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LOXO-101
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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). | ||
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C115977
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CHEMBL3545075
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46188928
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ARRY 470
Created by
admin on Tue Mar 06 11:02:27 UTC 2018 , Edited by admin on Tue Mar 06 11:02:27 UTC 2018
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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. | ||
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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.
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ACTIVE MOIETY |
Originator: Array BioPharma; Developer: Array BioPharma, Loxo Oncology; Class: Antineoplastic, Small molecule; Mechanism of Action: Tropomyosin-related kinase antagonist; Orphan Drug Status: Yes for Soft tissue sarcoma; New Molecular Entity: Yes; Highest Development Phases: Phase II for Solid tumours, Phase I for CNS cancer; Most Recent Events: 13 Jul 2016 LOXO 101 receives Breakthrough Therapy status for Solid tumours (Metastatic disease, Inoperable/Unresectable) in USA, 19 Apr 2016 Efficacy data from a phase I trial in CNS cancer released by Loxo Oncology, 17 Apr 2016 Interim efficacy and safety data from a phase I trial in Solid tumours presented at the Annual Meeting of American Association for Cancer Research (AACR-2016)
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ACTIVE MOIETY |
Drug: LOXO-101(Primary); Indications: Small cell lung cancer, Solid tumours; Focus: Adverse reactions, First in man, Therapeutic Use; Sponsor: Loxo Oncology; Most Recent Events: 17 Apr 2016 Results (n=43) presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting , according to a Loxo Oncology media release., 17 Apr 2016 Results (n=43) published in a Loxo Oncology media release. 15 Mar 2016 Updated data from this trial will be presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, according to a Loxo Oncology media release
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