UK-5099 | Mitochondrial pyruvate transporter inhibitor

UK-5099 (56396-35-1) is a potent inhibitor of the mitochondrial pyruvate carrier (MPC).¹ Rapidly increases glucose uptake in human monocytes.² Attenuates mitochondrial oxidative phosphorylation and increases glycolysis creating greater stem-like properties in LnCap prostate cancer cells.³ Blocks the neuroprotective action of L-lactate or pyruvate during glutamate-induced excitotoxicity.⁴ Inhibits pyruvate transport across the plasma membrane of trypanosomes (K_i=49 μM).⁵

References/Citations:

1) Shearman and Halestrap (1984), The concentration of the mitochondrial pyruvate carrier in rat liver and heart mitochondria determined with alpha-cyano-beta-(1-phenylindol-3-yl)acrylate; Biochem. J., 223 673
2) Divakaruni et al. (2013), Thiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier.; Proc. Natl. Acad. Sci. USA, 110 5422
3) Zhong et al. (2015), Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro; Oncotarget, 6 37758
4) Jourdain et al. (2016), L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade; Sci. Rep., 6 21250
5) Wiemer et al. (1995), The inhibition of pyruvate transport across the plasma membrane of the bloodstream form of Trypanosoma brucei and its metabolic implications; Biochem. J., 312 479