HCI-1046

HCI-1046 is a novel, small molecule inhibitor of the cytoplasmic GCN2 (EIF2AK4) kinase, developed by the Huntsman Cancer Institute and Biolexis Therapeutics. It is designed to target the nutrient stress response pathway in cancer cells, specifically in Acute Myeloid Leukemia (AML). By reversibly binding to the ATP site of GCN2, HCI-1046 prevents the inactivation of T-cells and the expansion of myeloid-derived suppressor cells (MDSCs) that typically occur in the nutrient-depleted tumor microenvironment. Preclinical studies have demonstrated that HCI-1046 has potent on-target activity, excellent oral bioavailability, and the ability to reinstate anti-tumor immunity and block tumor progression in vivo.