NCATS-SM1441

NCATS-SM1441 (also known as SM1441) is a potent, first-in-class, pyrazole-based small molecule inhibitor of lactate dehydrogenase (LDH). It was developed by the National Center for Advancing Translational Sciences (NCATS) in collaboration with academic institutions. NCATS-SM1441 potently inhibits both the LDHA and LDHB isoforms with nanomolar potency (IC50 of approximately 40 nM). By blocking the conversion of pyruvate to lactate and regenerating NAD+, NCATS-SM1441 disrupts the glycolytic pathway (aerobic glycolysis/Warburg effect) in cancer cells, leading to reduced lactate production, ATP depletion, and inhibition of tumor cell proliferation. It has been investigated in preclinical models of Ewing's sarcoma, pancreatic cancer, hepatocellular carcinoma (HCC), and acute kidney injury (AKI).