Repotrectinib (TPX-0005)

Description: Repotrectinib (TPX-0005, TPX0005) is a novel, oral, rationally-designed, highly potent inhibitor of ALK/ROS1/TRK with IC50 of 5.3 nM, 1.01 nM, 1.26 nM and 1.08 nM for SRC, WT ALK, ALK G1202R and ALK L1196M, respectively. It has potential anticancer activity. It effectively overcomes this primary resistance (IC50 100 nM in cell proliferation assay) with strong inhibition of the phosphorylation of EML4-ALK (IC50 13 nM) and the SRC substrate paxillin (IC50 107 nM). PX-0005 inhibits H2228 cell migration in a wound healing assay with similar activity to saracatinib. Overall, TPX-0005 has a highly favorable profile with ability to overcome multiple ALK resistance mechanisms including secondary mutations, bypass signaling activation, EMT, and warrants clinical investigation.

References: EBioMedicine. 2018 Mar; 29:112-127; Dayong Zhai, et al. AACR Cancer Res. 2016, 76(14 Suppl):

Related CAS: 1802220-02-5; 2058227-19-1

Ropotrectinib; TPX-0005; TPX 0005; TPX0005;

Chemical 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