telaglenastat + azacitidine

telaglenastat + azacitidine is a combination therapy comprising telaglenastat (CB-839), a potent and selective small-molecule inhibitor of the mitochondrial enzyme glutaminase (GLS), and azacitidine, a nucleoside metabolic inhibitor and hypomethylating agent. Developed by Calithera Biosciences, this combination was designed to treat hematologic malignancies, specifically relapsed or refractory acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). Telaglenastat works by inhibiting the conversion of glutamine to glutamate, thereby disrupting the tricarboxylic acid (TCA) cycle and glutathione production, which are vital for the survival and proliferation of glutamine-dependent cancer cells. Azacitidine incorporates into DNA and RNA, inhibiting DNA methyltransferases and leading to the re-expression of tumor suppressor genes and induction of cell differentiation. The combination aims to exploit metabolic vulnerabilities in leukemia cells while simultaneously reversing epigenetic silencing. Clinical development of this combination was primarily conducted in Phase 1 trials (e.g., NCT02071927), though further development was halted following the liquidation of Calithera Biosciences in 2023.

Other names

CB-839 + azacitidineCB-839 + 5-AZAtelaglenastat + Vidaza