Table 3. Physicochemical Properties and Rodent PK Data for 18 and 19 (IV/PO 1/10 mg/kg for rat and mouse).
| 18 | 19 | |
|---|---|---|
| cellular HCT116-IDH1R132H/+ IC50 (μM) | 0.015 | 0.039 |
| solubility at pH 6.8 (μM) | 422 | 124 |
| Caco-2 Papp (AB/BA) | 21/31 | 20/24 |
| MDR1-MDCK (AB/BA) | 6/57 | 11/39 |
| plasma protein binding (rat/mouse) | 95/92 | 98/98 |
| in vitro liver microsomal CLint (μL/min/mg) (rat/mouse) | 72/63 | 7.7/11 |
| in vivo plasma clearance (mL/min/kg) (rat/mouse) | 20/n.d.a | 2.6/5 |
| oral AUC (μM·h) (rat/mouse) | 15/n.d. | 180/172 |
| oral bioavailability (%) (rat/mouse) | 82/n.d. | 127/149 |
| brain to plasma (total) AUC ratio (rat) | <0.1 | 0.17 |
a
Not determined.