Koningic acid
Glyceraldehyde-3-phosphate dehydrogenase inhibitor / Koningic acid (KA) 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, Ki = 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
Biochemicals & reagents
74310-84-2
Heptelidic acid; BRN5091359; Avocettin
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
-20°C
TARGET: Dehydrogenase (GAPDH, GPDH, IMPDH, PHGDH, LDH, DHODH, ALDH, GDH, IDH, UGDH, DPD, DHPDH, KGDH, PDH, and MDH) -- PATHWAY: Carbohydrate metabolism; Warburg effect -- RESEARCH AREA: Oxidative stress -- DISEASE AREA: Cancer; Diabetes