ranosidenib

HMPL-306 (ranosidenib) is a novel, orally available small molecule that acts as a highly selective dual inhibitor of mutant isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2). Mutations in these enzymes are implicated as drivers in various cancers—including acute myeloid leukemia (AML), other hematological malignancies, gliomas, and solid tumors—by producing the oncometabolite 2-hydroxyglutarate (2-HG), which blocks cell differentiation and promotes malignant transformation. Unlike single isoform inhibitors that can lead to resistance via isoform switching between cytoplasmic mutant IDH1 and mitochondrial mutant IDH2, targeting both mutations with a dual inhibitor like ranosidenib may overcome this resistance. The drug has demonstrated promising safety and efficacy in early-phase clinical trials for relapsed or refractory AML with IDH1/IDH2 mutations. It is currently being evaluated in Phase III trials for AML[1][3][4][5][7].

Other names

ranosidenibHMPL-306HMPL306HMPL 306[14C] HMPL-306