Heptelidic Acid

Heptelidic acid (also known as koningic acid) is a sesquiterpene lactone antibiotic originally isolated from soil fungi including Gliocladium virens, Chaetomium globosum, and Trichoderma species. It exhibits selective antimicrobial activity against anaerobic bacteria such as Bacteroides fragilis. Mechanistically, heptelidic acid functions as an irreversible covalent inhibitor of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), thereby blocking glycolytic flux. In tumor models, GAPDH inhibition leads to suppression of cancer cell proliferation, including melanoma, through disruption of aerobic glycolysis. Additional studies demonstrate inhibition of tau fibrillization, although the primary validated molecular target remains GAPDH. Heptelidic acid serves as a canonical tool compound for studying glycolytic dependency in cancer and inflammatory biology.