heptelidic acid

Heptelidic acid, also known as avocettin or koningic acid, is a naturally occurring sesquiterpene lactone. It functions as a potent, specific, and irreversible inhibitor of Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH), a key enzyme in the glycolytic pathway. Its inhibitory action involves the covalent modification of a critical cysteine residue within the active site of GAPDH, thereby disrupting glycolysis, depleting cellular ATP, and inducing cytotoxicity, particularly in cancer cells that exhibit a high dependence on glycolysis (the Warburg effect). Beyond its primary role in glycolysis inhibition, heptelidic acid has also been observed to modulate the p38 MAPK pathway, induce apoptosis, and act as a selective inhibitor of mammalian DNA polymerases β and λ, as well as terminal deoxynucleotidyl transferase in family X of DNA polymerases. It is derived from fungi such as T. koningii and Aspergillus oryzae. Preclinical studies have demonstrated its anti-tumor efficacy in various cancer models, including pancreatic cancer, melanoma, pediatric B-cell acute lymphoblastic leukemia, and rhabdoid tumor of the kidney.

Other names

avocettinkoningic acid