TABLE 1 

Inhibitory activity of GSK1278863 against α-KG-dependent iron dioxygenases after a 30-minutes of enzyme with inhibitor preincubation

Kiapp values were calculated based on the equation: Ki = IC50/(1 + ([S]/Km) for a competitive inhibitor (Cheng and Prusoff, 1973).

EnzymeSubstrateα-KG Km (nM)IC50 ± S.D. (nM)Ki app (nM)nAssay Format
PHD1HIF1α CODDD71 ± 12a3.5 ± 0.61.8 ± 0.32FRET
PHD2HIF1α CODDD188 ± 14a22.2 ± 13.47.3 ± 4.510FRET
PHD3HIF2α CODDD7500 ± 2000a5.5 ± 5.11.8 ± 1.710FRET
FIHHIF-1α (D788-L822)32 ± 69800 ± 75003200 ± 2500214CO2 capture
CP4HProcollagen peptide53 ± 1>200,000>63,0007HPLC/14CO2
  • HPLC, high-performance liquid chromatography.

  • a Reported in Pappalardi et al. (2011).