Table 2. Key Properties of BRD2879.
| in vitro enzyme inhibition, IC50a | |
|---|---|
| IDH1-R132H | 0.05 μM |
| IDH1-R132C | 2.5 μM |
| IDH1-WT | >20 μM |
| IDH2-R140Q | >20 μM |
| thermal stabilizationb | |
|---|---|
| IDH1-R132H | 3.7 °C |
| IDH1-R132C | 1.4 °C |
| cell-based R-2HG suppression, EC50c | |
|---|---|
| HA1E-M-IDH1-R132H | 0.3 μM |
| mechanism of inhibition | |
|---|---|
| w.r.t. α-KG | competitive |
| w.r.t. Mg2+ | competitive |
| microsomal stability, t1/2f | |
|---|---|
| mouse | 0.7 min |
| human | 0.7 min |
| plasma protein bindingd | |
|---|---|
| mouse | 96.3% |
| human | 99.5% |
a
Geometric mean of at least three independent experiments.
b
Mean of three independent experiments, each with seven replicates.
c
Mean of three independent experiments, each with three replicates.
d
Mean of three replicates in one experiment.
e
Single experiment, includes 1% DMSO.
f
Single experiment, calculated from a 6-point curve over 1 h.