| A potent ATP-competitive inhibitor of tropomyosin-related kinases (TRK1, TRK2 and TRK3), members of the receptor tyrosine kinase family of neurotrophin receptors. Tumors with oncogenic TRK fusions are sensitive to larotrectinib, leading to reduced proliferation and tumor growth in patients with soft tissue sarcoma, triple-negative breast cancer and lung cancer. Larotrectinib, also known as ARRY-470 and 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. Synonyms: (3S)-N-[5-[(2R)-2-(2,5-Difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxy-1-pyrrolidinecarboxamide, ARRY 470, LOXO 101, Vitrakvi., (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide CAS Number: 1223403-58-4 Sulfate: 1223405-08-0 Molecular Weight: 428.44 Molecular Formula: C21H22F2N6O2 Appearance: White to off-white solid Purity: 98% Solubility: Soluble in DMSO, not in water Storage and Stability: Store at -20C under inert atmosphere. For maximum recovery of product, centrifuge the original vial prior to removing the cap. |
