Table 6. Partial In Vitro Profiling Data for 6d.
| parameter | result |
|---|---|
| protein binding (bound) | 99.7% human |
| 99.4% mouse | |
| 99.5% rat | |
| 98.7% dog | |
| 98.2% monkey | |
| mutagenicity | Ames negative |
| hERG (patch clamp) | IC50 > 30 μM |
| Na+ (patch clamp) | 13% @ 10 μM (1 and 4 Hz) |
| Ca+ (patch clamp) | 19% @ 10 μM |
| CYP inhibition (IC50)a | >12 μM 1A2, 2B6, 2D6, 2C19 |
| 3.2 μM 2C8 | |
| 5.7 μM 2C9 | |
| 11 μM 3A4 | |
| PAMPA permeability | 1836/1302 nm/s (pH 5.5/7.4) |
| Caco2 Permeability: | ND due to insufficient recovery |
| Aqueous solubility | <0.001 mg/mL |
| FaSSIF solubilityb | 14 μg/mL |
| FeSSIF solubilityc | 551 μg/mL |
| log D at pH 7.0 (HPLC) | 3.84 |
a
CYP = Cytochrome P450.
b
FaSSIF = Fasted state simulated intestinal fluid.
c
FeSSIF = Fed state simulated intestinal fluid; ND = not determined.