sirpiglenastat

Sirpiglenastat is a small molecule prodrug of 6-diazo‑5‑oxo‑L‑norleucine (DON), a broad-spectrum glutamine antagonist. It is designed to be preferentially activated within tumor cells, where it releases DON to irreversibly inhibit multiple enzymes involved in glutamine metabolism. This inhibition disrupts tumor cell proliferation and survival by blocking the conversion of exogenous glutamine into essential metabolites for energy production and macromolecule synthesis. The selective activation in tumors aims to spare healthy tissues from toxicity. In addition to direct antitumor effects, sirpiglenastat modulates the tumor microenvironment by enhancing T-cell proliferation and activation, increasing immune cell infiltration (including T cells, NK cells, and NKT cells), polarizing macrophages toward an M1 phenotype, reducing myeloid-derived suppressor cells (MDSCs), and decreasing immunosuppressive metabolites. These combined actions result in both direct cytotoxicity against cancer cells and stimulation of antitumoral immune responses[1][2][7][8].

Other names

(-)-sirpiglenastatSirpiglenastat [USAN](S)-isopropyl 2-((S)-2-acetamido-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoateL-norleucine, N-acetyl-L-tryptophyl–6-diazo–5–oxo-, 1-methylethyl esterPropan–2–yl (2S)–2–((N-acetyl-L tryptophyl)amino)–6-diazo–5 oxohexanoate