AY-9944

AY-9944 is a small molecule inhibitor of 7-dehydrocholesterol reductase (DHCR7), the enzyme responsible for the final step of cholesterol biosynthesis in the Kandutsch-Russell pathway. By blocking the conversion of 7-dehydrocholesterol to cholesterol, AY-9944 leads to an accumulation of 7-dehydrocholesterol and a deficiency in cholesterol, biochemical hallmarks that mimic Smith-Lemli-Opitz syndrome (SLOS). Historically developed by Ayerst Laboratories, it is primarily utilized as a research tool to study cholesterol homeostasis and to induce animal models of SLOS. Recent research, including studies presented at ASH 2025, has explored its potential in oncology, demonstrating cytotoxic effects in Acute Myeloid Leukemia (AML) cell lines, particularly those with FLT3-ITD mutations, by modulating intracellular cholesterol levels and influencing therapeutic response.

Other names

trans-1,4-bis(2-chlorobenzylaminomethyl)cyclohexane