Description
Ropotrectinib (TPX-0005; TP Therapeutics, San Diego, CA, USA) is a nextgeneration ROS1 inhibitor, a novel three-dimensional macrocyle with a much
smaller size (MW <370) than current ROS1 inhibitors. It was specifically
designed to overcome resistance mutations. Preclinical studies have shown activity
against gatekeeper and solvent mutations, including G2032R, D2033N, L2026M,
S1986F/Y, L1951R, and kinases involved in bypass signaling such as focal adhesion
kinase, SRC proto-oncogene, and non-receptor tyrosine kinase [102, 103].
General Description
Class: receptor tyrosine kinase;
Treatment: NSCLC;
Other name: TPX-0005
Biological Activity
Repotrectinib is a potent inhibitor targeting solvent-front mutations (SFMs) of ROS1, pan-TRK, and ALK. It effectively inhibits the kinase activity of wild-type ROS1, TRKA-C, and ALK, along with their SFMs, with IC50 values ranging from 0.071 to 4.46 nM. The compound shows high potency against ROS1 and TRKA-C, with approximately 15-fold selectivity over ALK.
Clinical Use
Repotrectinib has advantage with central nervous system (CNS) penetration, aimed to target both wide-type (WT) and solvent-front mutations (SFM) kinases and other resistance mutations including ROS1-G2032R and ROS1-D2033N, TRKA-G595R, TRKB-G639R, TRKC-G623R, and ALK-G1202R.
target
Primary targets: NTRK, ROS, ALT
;