AS71

AS71 is a small molecule inhibitor of adenylosuccinate synthetase 2 (ADSS2), an enzyme that catalyzes the rate-limiting step in the biosynthesis of adenosine monophosphate (AMP) from inosine monophosphate (IMP). Identified through fragment-based virtual screening, AS71 has been shown to physically bind ADSS2 and induce thermal stability shifts in cellular contexts. In preclinical models of acute myeloid leukemia (AML), AS71 sensitizes cells to mitochondrial apoptosis induced by BH3 mimetics, such as venetoclax (Bcl-2 inhibitor) and S63845 (Mcl-1 inhibitor). This sensitization is mediated by the depletion of AMP and subsequent repression of AMPK signaling, which increases mitochondrial vulnerability.