Heptelidic acid (Koningic acid) is a sesquiterpenoid lactone antibiotic derived from the probiotic fungus Aspergillus oryzae, a selective GAPDH inhibitor. It downregulates caspase to inhibit etoposide-induced apoptosis. Heptelidic acid inhibits tau fibrillation in a concentration-dependent manner and exerts antitumor effects on extra-intestinal melanoma by controlling glyceraldehyde-3-phosphate dehydrogenase activity.

Caspase-3:40 μM, HEK293T cells (T. koningii KAr-GAPDH):5 μM

Heptelidic acid is a sesquiterpenoid antibiotic found in the culture filtrates of three different fungal strains isolated from soil samples. The process of its production involves culture, fermentation, isolation, and characterization of the organisms. [1]
Heptelidic acid prevents etoposide-induced apoptosis in human leukemia U937 cells. [2] The IC50 value for the inhibitory effect of Heptelidic acid on caspase-3 activity in U937 cells after 8 h of etoposide treatment was 40 μM. [2]
As a natural product extracted from Trichoderma, Heptelidic acid can directly bind to the active site of human GAPDH.[2] Heptelidic acid has been shown to inhibit caspase-3 activity in T. koningii KA. Cells expressing T. koningii KAr-GAPDH were able to successfully restore the survival of Heptelidic acid-treated human cells. HEK293T cells treated with 0-200 μM Heptelidic acid showed complete survival with an IC50 of 5 μM in the presence of T. koningii KAr-GAPDH.[2] Heptelidic acid is a natural product extracted from Trichoderma species. Its IC50 was 5 μM. [3]

In 6-week-old female Foxn1nu mice bearing BT-474 tumors, 1, 2.5, 5, and 10 mg/kg of Heptelidic acid were administered by intraperitoneal injection once a day for 24 hours. Based on behavioral monitoring and adverse events (e.g., hemolysis, hematuria, and anemia) at high doses, 1 mg/kg was identified as the maximum tolerated dose (MTD). [3]