Koningic acid | Glyceraldehyde-3-phosphate dehydrogenase inhibitor

Koningic acid (KA; 74310-84-2) is a potent and selective inhibitor of glyceraldehyde-3-phosphate dehydrogenase (GAPDH).¹  Inhibition is irreversible and proceeds via nucleophilic attack of an active site cysteine on the epoxide moiety², K_i = 1.1 μM for rabbit muscle GAPDH³. KA can selectively kill high-glycolytic cancer cells via glucose dependent ATP depletion.⁴ Has been used in a predictive model for selective targeting of the Warburg effect, the most prominent hallmark of cancer cell metabolism.⁵

References/Citations

1) Endo et al. (1985), Specific inhibition of glyceraldehyde-3-phosphate dehydrogenase by koningic acid (heptelidic acid); J. Antibiot., 38 920
2) Sakai et al. (1991), Identification of koningic acid (heptelidic acid)-modified site in rabbit muscle glyceraldehyde-3-phosphate dehydrogenase; Biochim. Biophys. Acta, 1077 192
3) Sakai et al. (1988), Inactivation of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase by koningic acid; Biochim. Biophys. Acta, 952 297
4) Kumagai et al. (2008), Glucose-dependent active ATP depletion by koningic acid kills high-glycolytic cells; Biochem. Biophys. Res. Commun. 365 362
5) Liberti et al. (2017), A Predictive Model for Selective Targeting of the Warburg Effect through GAPDH Inhibition with a Natural Product; Cell Metab., 26 648