TRK II-IN-1 is a potent type II inhibitor of tropomyosin receptor kinases (TRK), demonstrating inhibitory half-maximal inhibitory concentrations (IC50s) of 3.3, 6.4, 4.3, and 9.4 nM against TRKA, TRKB, TRKC, and the mutant TRKA G667C, respectively. Additionally, this compound 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].

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

TRK II-IN-1（化合物12d）（1 μM）对VEGFR2、RET、FLT3的激酶抑制活性超过90%，并对Kit、CSF1R、DDR1及DDR2展现出近70%的抑制率[1]。TRK II-IN-1（72小时）抑制Ba/F3-CD74-TRKA、Ba/F3-ETV6-TRKB及Ba/F3-ETV6-TRKC细胞，相应IC50值分别为26.1、44.7和15.7 nM[1]。此外，TRK II-IN-1（72小时）抑制携带野生型、xDFG及溶剂前（SF）突变TRK融合蛋白质的Ba/F3细胞系增殖，IC50值范围为2.6至143.3 nM[1]。TRK II-IN-1（0.4-500 nM；48小时）促进Ba/F3-CD74-TRKA和Ba/F3-CD74-TRKA G667C细胞的凋亡[1]。同一化合物（0.4-500 nM；24小时）在Ba/F3-CD74-TRKA及Ba/F3-CD74-TRKA G667C细胞中诱导G0/G1期细胞周期阻滞[1]。并且，TRK II-IN-1（0.8-500 nM；6小时）以剂量依赖方式抑制TRKA及TRKA G667C激酶的磷酸化以及其下游的AKT、ERK和PLCγ1[1]。