crelosidenib

Crelosidenib (LY3410738) is an orally available, first-in-class covalent inhibitor targeting mutant forms of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2). It was developed to treat cancers—both solid tumors and hematologic malignancies—that harbor mutations in the IDH1 or IDH2 genes. Crelosidenib binds covalently to a specific cysteine residue in the allosteric binding pocket of mutant IDH1 enzymes, inhibiting their activity and blocking production of the oncometabolite (R)-2-hydroxyglutarate ((R)-2HG), which drives tumorigenesis. The drug was designed to overcome resistance mechanisms seen with reversible IDH inhibitors by maintaining potency against certain acquired resistance mutations. Despite its promising mechanism and brain penetration properties, clinical development for both solid tumors and blood cancers has been discontinued following limited efficacy in early-phase trials[3][4][5][6][7][8].

Other names

crelosidenibLY3410738LY-3410738LY 3410738