Heptelidic acid

Heptelidic acid (Koningic acid) is a sesquiterpene antibiotic[1]. Heptelidic acid inhibits Etoposide-induced apoptosis via downregulation of caspases[2]. Koningic acid (KA) is a specific GAPDH inhibitor with an IC50of 90 μM[3].

Research Areas >> Cancer

Research Areas >> Infection

Signaling Pathways >> Apoptosis >> Caspase

Caspase-3

Heptelidic acid is a sesquiterpene antibiotic, found in the culture filtrate of three different strains of fungi isolated from soil samples. Heptelidic acid produces organisms, fermentation, isolation and characterization[1]. Heptelidic acid inhibits Etoposide-induced apoptosis in human leukemia U937 cells[2].Heptelidic acid inhibits caspase- 3 induction in U937 cells with an IC50 value of 40 μM after 8 h of Etoposide treatment[2]. Heptelidic acid (Koningic acid; KA), a natural product obtained from the Trichoderma fungus, can directly bind to the active site of human GAPDH. The expression of T. koningii KAr-GAPDH successfully rescued cell viability in human cells treated with Heptelidic acid. HEK293T cells expressing T. koningii KAr-GAPDH exhibited complete cell viability after treatment with 0-200 μM Heptelidic acid with the IC50=5 μM[3]. Cell Viability Assay[3] Cell Line: HEK293T cells expressing KAr-GAPDH or EV (top left) Concentration: 0.1, 1, 10, 100, 1000 μM Incubation Time: 24 hours Result: IC50=5 μM.

Heptelidic acid (Koningic acid; KA) is bioavailable and induces dynamic changes to glycolysis in vivo[3]. Animal Model: 6-week old female Foxn1nu mice bearing BT-474 tumor[3] Dosage: 1, 2.5, 5, and 10 mg/kg Administration: Daily intraperitoneal (IP) injections, 24 hours Result: 1 mg/kg was determined to be the maximum tolerated dose (MTD) based upon behavioral monitoring and adverse events at higher doses (hemolysis, hematuria, and anemia).

[1]. Y Itoh, et al. A new sesquiterpene antibiotic, heptelidic acid producing organisms, fermentation, isolation and characterization. J Antibiot (Tokyo). 1980 May;33(5):468-73.

[2]. Jin Hee Kim, et al. Heptelidic acid, a sesquiterpene lactone, inhibits Etoposide-induced apoptosis in human leukemia U937 cells. J Microbiol Biotechnol. 2009 Aug;19(8):787-91.

[3]. Maria V Liberti, et al. A Predictive Model for Selective Targeting of the Warburg Effect through GAPDH Inhibition with a Natural Product. Cell Metab. 2017 Oct 3;26(4):648-659.e8.