NCIt definition : An orally available inhibitor of isocitrate dehydrogenase type 1 (IDH1; IDH-1; IDH1
[NADP ] soluble) with a mutation at arginine (R) 132, IDH1(R132), with potential antineoplastic
activity. Upon administration, olutasidenib specifically inhibits IDH1(R132), 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
IDH(R132). IDH1(R132) mutations are highly expressed in certain malignancies, including
gliomas; they initiate and drive cancer growth by both blocking cell differentiation
and catalyzing the formation of 2HG.;