Definition

An orally available inhibitor of isocitrate dehydrogenase type 1 (IDH1; IDH-1; IDH1 [NADP+] soluble) mutant forms, with potential antineoplastic activity. Upon administration, IDH1 inhibitor KY100001 specifically binds to and inhibits certain mutant forms of IDH1, 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 IDH1 mutations. IDH1 mutations are highly expressed in certain malignancies; they initiate and drive cancer growth by both blocking cell differentiation and catalyzing the formation of 2HG.