TPX-0005

TPX-0005 is a multi-kinase inhibitor that inhibits TrkA, TrkB, and TrkC (IC50s = 0.83, 0.05, and 0.1 nM, respectively) as well as C-ros oncogene 1 (ROS1, IC50 = 0.07 nM). It inhibits a variety of other kinases, including ALK, JAK2, LYN, Src, and FAK (IC50s = 1.04, 1.04, 1.66, 5.3, and 6.96 nM, respectively). It inhibits proliferation of PC-9, H1975, 11-18, HCC4006, and HCC827 lung cancer cells (IC50s = 100, 100, 150, 148, and 430 nM, respectively) with additive or synergistic effects when used in combination with gefitinib (Cay-13166), afatinib (Cay-11492), PF-299804 (dacomitinib, Cay-9001879), or osimertinib. TPX-0005 (30 mg/kg) reduces tumor growth in PC-9 and H1975 mouse xenograft models and potentiates the effect of osimertinib in these models.Formal Name: (7S,13R)-11-fluoro-6,7,13,14-tetrahydro-7,13-dimethyl-1,15-etheno-1H-pyrazolo[4,3-f][1,4,8,10]benzoxatriazacyclotridecin-4(5H)-one. CAS Number: 1802220-02-5. Synonyms: Repotrectinib. Molecular Formula: C18H18FN5O2. Formula Weight: 355.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 1 mg/ml, DMSO: 0.2 mg/ml. lambdamax: 222, 258 nm. SMILES: C[C@@H](NC1=NC2=C3C=NN2C=C1)C4=CC(F)=CC=C4O[C@@H](C)CNC3=O. InChi Code: InChI=1S/C18H18FN5O2/c1-10-8-20-18(25)14-9-21-24-6-5-16(23-17(14)24)22-11(2)13-7-12(19)3-4-15(13)26-10/h3-7,9-11H,8H2,1-2H3,(H,20,25)(H,22,23)/t10-,11+/m0/s1. InChi Key: FIKPXCOQUIZNHB-WDEREUQCSA-N.