PGP inhibitor CP1 is a specific small-molecule phosphoglycolate phosphatase (PGP) inhibitor with IC50 of 0.39 uM (hPGP), blocks PGP-dependent glycolytic flux in mammalian cells.
PGP inhibitor CP1 CP1 potently inhibited the activity of both human and murine PGP towards PG, also inhibited the activity of murine PGP towards the generic phosphatase substrate para-nitrophenylphosphate (pNPP).
PGP inhibitor CP1 also effectively inhibited the dephosphorylation of 2-phospho-L-lactate (2PL), 4-phosphoerythronate (4PE) and glycerol 3-phosphate (G3P).
PGP inhibitor CP1 interacted with the PGP cap domain (ITC Kd=0.78 uM), and bound to both the cap and the core domain of PGP.
PGP inhibitor CP1 displayed remarkable selectivity over 12 other mammalian haloacid dehalogenase (HAD) phosphatases (PP2B, PTP1B, intestinal alkaline phosphatase, etc.).
PGP inhibitor CP1 impairs glycolytic flux, impairs PGP-dependent cell proliferation, and induces PGP-dependent lipid droplet accumulation in HT1080 cells.
PGP inhibitor CP1 is a useful tool compound to probe the functional consequences of acute PGP inhibition, phenocopies effects of cellular PGP-deficiency.