Table 3.
Racemic 2OG derivative 11 is a more efficient R172K IDH2 inhibitor than N-oxalylglycine
| Entry | a2OG derivative | IDH1/2 variant | bIC50 [μM] |
|---|---|---|---|
| A |  |
cR132H IDH1 | 188 ± 26 |
| dR172K IDH2 | 161 ± 25 | ||
| eR140Q IDH2 | 621 ± 69 | ||
| B |  |
cR132H IDH1 | 1104 ± 62 |
| dR172K IDH2 | 84 ± 14 | ||
| eR140Q IDH2 | 1652 ± 206 |
a 2OG derivative 11 was prepared as a racemic mixture according to a reported procedure (22).
b determined using absorbance assays as described in the Experimental procedures section, mean of two independent runs each composed of technical quadruplicates (n = 2; mean ± SD).
c-e using 0.03 μM IDH1/2 variant, 50 μM NADPH, and (c) 1.5 mM 2OG, (d) 1.0 mM 2OG, or (e) 6.0 mM 2OG in reaction buffer (100 mM Tris, pH 8.0, 0.005%v/v tween-20, 0.1 mg/mL BSA, 0.2 mM DTT, 10 mM MgCl2, 150 mM NaCl).