CB-839 + capecitabine

CB-839 + capecitabine is a combination therapy consisting of telaglenastat (CB-839), a first-in-class, highly selective small molecule inhibitor of glutaminase (GLS), and capecitabine, an oral prodrug that is converted to 5-fluorouracil (5-FU) in the body. Telaglenastat inhibits GLS, thereby blocking the conversion of glutamine to glutamate—a key step in cancer cell metabolism—leading to reduced tumor growth and increased oxidative stress. Capecitabine is metabolized into 5-FU, which inhibits thymidylate synthase and disrupts DNA synthesis in rapidly dividing cells. Preclinical studies have shown that this combination has synergistic antitumor activity, particularly in PIK3CA-mutant colorectal cancers. Mechanistically, CB-839 increases reactive oxygen species and upregulates uridine phosphorylase 1 (UPP1), enhancing the activation of 5-FU from its prodrug form and increasing cytotoxicity against cancer cells. Clinical trials indicate that this combination is well tolerated at biologically active doses[1][4].

Other names

telaglenastat + capecitabineglutaminase inhibitor CB-839 + capecitabine