PGMI-004A

PGMI-004A is a small molecule inhibitor of phosphoglycerate mutase 1 (PGAM1), an enzyme that plays a critical role in coordinating glycolysis and anabolic biosynthesis to support rapid tumor growth. By inhibiting PGAM1, the compound increases intracellular levels of 3-phosphoglycerate (3-PG) and decreases 2-phosphoglycerate (2-PG), which in turn inhibits 6-phosphogluconate dehydrogenase (6PGD) and reduces flux through the pentose phosphate pathway (PPP). This metabolic disruption attenuates cancer cell proliferation and tumor growth in various models, including xenograft mice and primary human leukemia cells (AML, CML, and B-ALL), while showing minimal toxicity to normal cells.