LOXO-195

LOXO-195 is an inhibitor of the receptor tyrosine kinases TrkA and TrkC (IC50s = 0.6 and G595R, TrkAG667C, TrkCG623R, and TrkCG696A (IC50s = 2, 9.8, 2.3, and 50 value of 1.9 nM. It selectively inhibits proliferation of Trk fusion-positive K12, CUTO-3, and MO-91 cell lines (IC50s = =5 nM) over Trk fusion-negative cell lines when used at concentrations up to 10 µM. LOXO-195 (>30 mg/kg) reduces tumor growth in TrkA-dependent KM12, as well as NIH 3T3 DeltaTrkA, DeltaTrkA + TrkAG595R, and DeltaTrkA + TrkAG667C mouse xenograft models.Formal Name: (3aR,10R)-5-fluoro-1,2,3,3a,8,9,10,11-octahydro-10-methyl-12H-15,17-ethenopyrazolo[3,4-d]pyrido[2,3-k]pyrrolo[2,1-m][1,3,7]triazacyclotridecin-12-one. CAS Number: 2097002-61-2. Synonyms: Selitrectinib. Molecular Formula: C20H21FN6O. Formula Weight: 380.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 12 mg/ml, DMSO: 5 mg/ml, Ethanol: 3 mg/ml. lambdamax: 228, 265 nm. SMILES: O=C(N[C@H](C)CCC1=NC=C(F)C=C1[C@]2([H])N3CCC2)C4=C5N(N=C4)C=CC3=N5. InChi Code: InChI=1S/C20H21FN6O/c1-12-4-5-16-14(9-13(21)10-22-16)17-3-2-7-26(17)18-6-8-27-19(25-18)15(11-23-27)20(28)24-12/h6,8-12,17H,2-5,7H2,1H3,(H,24,28)/t12-,17-/m1/s1. InChi Key: OEBIHOVSAMBXIB-SJKOYZFVSA-N.