Synthesis, in silico studies, and in vitro evaluation of novel isoindigo inhibitors targeting wild-type and D835Y mutant FLT3

Fourteen isoindigos were synthesized; four inhibit FLT3 at nanomolar concentrations, 3 being the best dual inhibitor (243 nM wild-type, 121 nM D835Y), 8 the best on wild-type FLT3 at 180 nM, and both with stable binding over 1 µs of simulation.