Table 3. DMPK and Safety Properties of BI Compounds.
| properties | 1 | 2 | 9 | |
|---|---|---|---|---|
| log D | 1.8 | 1.9 | 2 | |
| solubility (μM) | 170 | 152 | >1000 | |
| human CLpred microsomes (% LBF) | 19 | 25 | 61 | |
| rat CLpred hepatocytes (% LBF) | 14 | 25 | 52 | |
| human PPB (% free) | 22 | 32 | 31 | |
| Caco-2 A-B/B-A (1 × 10–6 cm/s) | 11/30 | 37/14 | 26/22 | |
| CYPb inhibition (μM) | >50 | >50 | >50 | |
| hERG (μM) | >33 | >33 | >33 | |
| secondary pharmacology hits | no significant hitsc | NDa | ||
| rat PK | CL (mL/min/kg) | 27 | 48 | ND |
| F (%) | 100 | 114 | ND | |
a
ND: not determined.
b
CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4.
c
Panel of ∼28 high severity targets (binding and functional data): IC50, >100 or >30 μM.