Table 2.
Targeted inhibitor potency and profile goals observed for the selected representative compound, COR-500015, for in vivo trials.
| Target activity | Activity of selected compound | |
|---|---|---|
| CYP17 | IC50 < 100 nM | IC50 = 8 nM |
| CYP11B1 | IC50 < 100 nM | IC50 =12 nM |
| CYP21 | IC50 < 100 nM | IC50 = 208 nM |
| Off-target counter screens | ||
| CYP19 | 50× CYP17 | IC50 = 350 nM |
| Bile Acid (CYP7A surrogate) | 100× CYP17 | IC50 = 880 nM |
| CYP450 34A > 50% @ 1 mM | IC50 (nM) | IC50 = 109 nM |
| CYP450 2D6 > 50% @ 1 mM | >50% @ 1 μM | Data not given |
| CYP450 2C9 > 50% @ 1 mM | >50% @ 1 μM | Data not given |
| Pharmaceutical profiling/ADME | ||
| Solubility >5 μM | μMolar | Data not given |
| Molecular Weight | <500 AMU | 545 AMU |
| ClogP | <5 | 4.2 (logP) |
| TPSA | <140 | 69 |
| Cytotoxicity in HerG2 | 10% @1 μM | Data not given |
| Caco-2-permeability (A-B, B-A) | >20 (10–6 cm/s) | Data not given |
| Guinea pig liver microsomal stability | >30 min | Data not given |
| Plasma stability | >30 min | Data not given |
| Plasma protein binding | >30 min | Data not given |
| Guinea pig bioavailability | >25% | Data not given |
| Guinea pig t1/2 | <4 h | 6 h |