TRK-IN-32 is a potent TRK inhibitor. It significantly suppresses TRKWT, TRKG595R, and TRKG667C with IC50 values of 0.08 nM, 2.14 nM, and 0.68 nM, respectively. Additionally, TRK-IN-32 exhibits antiproliferative activity against various Ba/F3 cell lines transformed by wild-type, xDFG mutant, solvent front, and gatekeeper mutant TRK fusion proteins. It also induces apoptosis in Ba/F3-TRKAWT and Ba/F3-TRKAG667C cells. TRK-IN-32 is applicable in research on various cancers, including thyroid cancer and secretory breast cancer.

TRK-IN-32 (Compound 15m) demonstrates good stability in human liver microsomes (t 1/2 = 33.8 minutes). It exhibits antiproliferative activity against the Ba/F3 cell line with IC 50 values of 1.24 nM (Ba/F3-ETV6-TRKA WT), 0.35 nM (Ba/F3-ETV6-TRKB WT), 24.26 nM (Ba/F3-LMNA-TRKA G595R), 10.24 nM (Ba/F3-LMNA-TRKA G667C), and 1.06 nM (Ba/F3-LMNA-TRKA F589L). At relatively low concentrations (0-10 nM), TRK-IN-32 effectively blocks autophosphorylation of TRKA WT and TRKA G667C and phosphorylation of downstream molecules AKT, PLCγ1, and ERK in Ba/F3 cells expressing TRKA WT and TRKA G667C fusion mutants. Additionally, TRK-IN-32 strongly induces apoptosis in Ba/F3-CD74-TRKA and Ba/F3-CD74-TRKA G667C cells when used at concentrations of 0-500 nM for 48 hours.