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. 2024 Mar 27;10(13):eado7808. doi: 10.1126/sciadv.ado7808

Fig. 1. Effect of glutamine antagonists on cancer cell metabolism and the immune microenvironment.

Fig. 1.

(A) DRP-104 and CB-839 have distinct metabolic effects. DRP-104 inhibits amidotransferases that contribute to purines and other biosynthetic intermediates (dashed box). CB-839 suppresses flow into the TCA cycle. DRP-104’s blockade of purine synthesis is most responsible for tumor cell growth suppression. (B) In Keap1-mutant lung cancers, DRP-104 stimulates antitumor immunity by modulating several T cell subsets in the tumor microenvironment. Gln, glutamine; Glu, glutamate; α-KG, α-ketoglutarate; GSH, glutathione; GLS, glutaminase; PPAT, phosphoribosyl pyrophosphate amidotransferase; PFAS, phosphoribosylformylglycinamidine synthase; GMPS, guanosine 5'-monophosphate synthase; ASNS, asparagine synthetase; GFPT1, glutamine-fructose-6-phosphate transaminase-1; CTPS, cytidine 5′-triphosphate synthetase; Tregs, regulatory T cells. Credit: Ashley Mastin/Science Advances.