In vitro activity: Vorasidenib (formerly known as AG-881) is a selective and orally bioavailable inhibitor of mutated forms of both isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) with potential anticancer activity. IDH is an essential enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle. Recurrent mutations in IDH1 or IDH2 are prevalent in several cancers including glioma, acute myeloid leukemia (AML), cholangiocarcinoma and chondrosarcoma. As a Pan-IDH1/2 inhibitor, AG881 potently and selectively inhibits mutant IDH protein and induce cell differentiation in in vitro and in vivo models. Upon administration, pan-IDH mutant inhibitor AG-881 specifically inhibits mutant forms of IDH1 and IDH2, thereby inhibiting the formation of the oncometabolite 2-hydroxyglutarate (2HG) from alpha-ketoglutarate (a-KG) ,which prevents 2HG-mediated signaling and leads to both an induction of cellular differentiation and an inhibition of cellular proliferation in tumor cells expressing IDH mutations.

Kinase Assay: Vorasidenib (formerly known as AG-881) is a selective and orally bioavailable inhibitor of mutated forms of both isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) with potential anticancer activity. IDH is an essential enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle. Recurrent mutations in IDH1 or IDH2 are prevalent in several cancers including glioma, acute myeloid leukemia (AML), cholangiocarcinoma and chondrosarcoma. As a Pan-IDH1/2 inhibitor, AG881 potently and selectively inhibits mutant IDH protein and induce cell differentiation in in vitro and in vivo models. Upon administration, pan-IDH mutant inhibitor AG-881 specifically inhibits mutant forms of IDH1 and IDH2, thereby inhibiting the formation of the oncometabolite 2-hydroxyglutarate (2HG) from alpha-ketoglutarate (a-KG) ,which prevents 2HG-mediated signaling and leads to both an induction of cellular differentiation and an inhibition of cellular proliferation in tumor cells expressing IDH mutations.

Cell Assay: Pan-IDH1/2 inhibitor AG881 selectively inhibits mutant IDH protein and induce cell differentiation in in vitro and in vivo models. Upon administration, pan-IDH mutant inhibitor AG-881 specifically inhibits mutant forms of IDH1 and 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 IDH mutations.