NCIt definition : An orally available pan-inhibitor of mutant forms of the metabolic enzyme isocitrate
dehydrogenase type 1 (IDH1; IDH-1; IDH1 [NADP ] soluble), including forms with mutations
of arginine 132 (IDH1(R132)), with potential antineoplastic activity. Upon administration,
pan-mutant-IDH-1 inhibitor BAY-1436032 specifically inhibits the activity of IDH1
mutant forms, which prevents 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 mutant forms. IDH1 mutations, including IDH1(R132)
mutations, are highly expressed in certain malignancies; they initiate and drive cancer
growth by both blocking cell differentiation and catalyzing the formation of 2HG.;
Semantic type(s)