BI4916

BI4916 is a potent and selective small molecule inhibitor of phosphoglycerate dehydrogenase (PHGDH), the enzyme that catalyzes the first and rate-limiting step of the de novo serine biosynthesis pathway. Developed by Boehringer Ingelheim, BI4916 is utilized as a chemical probe to investigate the role of serine metabolism in various cancers, particularly acute myeloid leukemia (AML). Research indicates that BI4916 can synergize with asparaginase therapies (such as crisantaspase) by blocking the compensatory upregulation of serine synthesis that leukemia cells use to survive nutrient deprivation. This combination treatment impairs protein synthesis and reduces intracellular glutathione levels, leading to enhanced anti-proliferative effects and cell death in AML models.