TRK II-IN-1 is a potent type II inhibitor of tropomyosin receptor kinases (TRK), with IC50 values of 3.3, 6.4, 4.3, and 9.4 nM against TRKA, TRKB, TRKC, and the mutant TRKA G667C, respectively. It also exhibits IC50 values of 1.3 nM against FLT3, 9.9 nM against RET, and 71.1 nM against VEGFR2. TRK II-IN-1 primarily serves as a research tool for studying TRK-driven cancers [1].

TrkA:3.3 nM, TrkB:6.4 nM, TrkC:4.3 nM, FLT3:1.3 nM, RET:9.9 nM, VEGFR2:71.1 nM, TrkA G667C:9.4 nM

TRK II-IN-1 (compound 12d) demonstrated significant kinase inhibition, achieving over 90% inhibition of VEGFR2, RET, and FLT3, and approximately 70% inhibition of Kit, CSF1R, DDR1, and DDR2 at 1 μM [1]. The compound effectively inhibited growth in Ba/F3 cell lines Ba/F3-CD74-TRKA, Ba/F3-ETV6-TRKB, and Ba/F3-ETV6-TRKC at 72 hours, with IC50 values of 26.1, 44.7, and 15.7 nM respectively [1]. It also suppressed proliferation in Ba/F3 cells with various TRK fusion proteins (wild type and mutant), showing IC50 values of 2.6-143.3 nM [1]. TRK II-IN-1 induced apoptosis in Ba/F3-CD74-TRKA and Ba/F3-CD74-TRKA G667C cells within 48 hours at concentrations of 0.4-500 nM [1], caused G0/G1 cell cycle arrest in the same cells over 24 hours [1], and dose-dependently suppressed phosphorylation of TRKA, TRKA G667C, AKT, ERK, and PLCγ1 after 6 hours of treatment at 0.8-500 nM [1].