BAY-1436032 is a highly selective, potent and orally available inhibitor of mutant Isocitrate Dehydrogenase 1 (mIDH1). Optically pure BAY-1436032 is a double-digit nanomolar and selective pan-inhibitor of the enzymatic activity of various IDH1-R132X mutants in vitro and displayed potent inhibition of “oncometabolite” 2-hydroxyglutarate (2-HG) release (nM range) in patient derived and engineered cell lines expressing different IDH1 mutants. In line with the proposed mode of action, a concentration-dependent lowering of 2HG was observed in vitro accompanied by differentiation of maturation of mIDH1 tumor cells. It also showed a favorable selective profile against wIDH1/2 and a large panel of off-target proteins. Demonstrated a single agent in vivo efficacy in mIDH1 patient derived glioma and intrahepatic cholangiocarcinoma solid tumor model. BBB penetrant.
>99 % by chiral HPLC
Room temperature for short term or -20ºC for 3 years.