TPX-0005, a novel ALK/ROS1/TRK inhibitor, effectively inhibited a broad spectrum of mutations including solvent front ALK G1202R, ROS1 G2032R and TRKA G595R mutants

An abstract of a study by Cui et al on TPX-0005, a novel ALK/ROS1/TRK inhibitor, which effectively inhibited a broad spectrum of mutations including solvent front ALK G1202R, ROSI 02032R and IRKA G595R mutants, is presented. Results showed TPX-0005 potently inhibited both wild type and mutant ALK/ROS1/TRKs, including gatekeeper and solvent front mutations. TPX-0005 showed low nano-molar activities against CD74-ROS1 G2032R (IC50 8.4 nM), LMNA-TRKA G595R (IC50 0.4 nM), TEL-TRKB G639R (IC50 1.9 riM) and TEL-TRKC G623R (IC50 0.4 nM) in Ba/F3 cell proliferation assays. TPX-0005 also demonstrated desired drug-like properties and good safety profile, and is actively pursued in the clinical development.