ASX-173

ASX-173 is a selective, cell-penetrant small molecule inhibitor of human asparagine synthetase (ASNS), the ATP-dependent enzyme responsible for intracellular de novo asparagine biosynthesis from aspartate and glutamine. By binding with high affinity to a unique hydrophobic pocket in the C‑terminal synthetase domain formed by AMP, Mg2+, and pyrophosphate in the ASNS/Mg2+/ATP complex, ASX-173 acts as an uncompetitive enzyme inhibitor, lowering intracellular asparagine levels, activating the amino acid starvation–driven integrated stress response (ISR), and suppressing cell growth in HEK-293A cell models.[2][3] Preclinical work positions ASX-173 as a research tool and potential lead compound for targeting asparagine metabolism in asparaginase-resistant acute lymphoblastic leukemia, acute myeloid leukemia, colorectal cancer, sarcomas, and other tumors that rely on ASNS activity for survival under nutrient stress.[1][2][3][5]