Table 3. Key Properties of Lead Compound 27.
| in vitro enzyme inhibition, IC50a | |
|---|---|
| PfDHODH (μM) | 0.012 |
| HsDHODH (μM) | >50 |
| plasma protein bindingb | |
|---|---|
| mouse (%) | 99.3 |
| human (%) | >99.0 |
| mouse PKc | |
|---|---|
| t1/2 (h) | 15.2 |
| C0 (μM) | 4.9 |
| Cmax (μM) | 16.9 |
| DNAUC0-inf (μM·h) | >54.3 |
| Vss (L/kg) | 0.37 |
| CL (mL/min/kg) | 0.40 |
| F (%) | 94 |
a
Mean of a single experiment in triplicate.
b
Single experiment, calculated from a six-point curve over 1 h.
c
t1/2, terminal half-life; C0, initial serum concentration at t = 0; Cmax, peak serum concentration; DNAUC0-inf, dose-normalized area under the plasma concentration vs time curve following PO dosing; Vss, volume of distribution at steady state; CL, plasma clearance; F%, bioavailability. IV dosing in 5% DMSO/10% cremophor/85% H2O at 0.25 mg/mL (1 mg/kg). PO dosing in 70% PEG300/30% (5% dextrose in H2O) at 0.50 mg/mL (5 mg/kg). n = 3 mice in both IV and PO groups.