Definition

An orally bioavailable inhibitor of mutated mitochondrial enzyme isocitrate dehydrogenase type 2 (IDH2; IDH-2), with potential antineoplastic activity. Upon oral administration, IDH2 mutant inhibitor TQB3455 specifically inhibits mutated IDH2, thereby inhibiting the formation of the oncometabolite 2-hydroxyglutarate (2HG) from alpha-ketoglutarate (a-KG). This prevents 2HG-mediated signaling and leads to both an induction of cellular differentiation and an inhibition of cellular proliferation in tumor cells expressing mutated IDH2. IDH2 is mutated in a variety of cancers, and mutated IDH2 initiate and drive cancer growth by catalyzing the formation of 2HG and blocking cell differentiation.