Table 1.
ADME profile of compound 1(S), the σ1 protein agonist used in these studies.
| Values | Experimental conditions | |
|---|---|---|
| Bioavailability | ||
| Aqueous solubility | 278 μM | PBS, pH 7.4 |
| logD | 2.15 | n-octanol/PBS, pH 7.4 |
| P-gp inhibition | 10.3% | 1 μM |
| Plasma protein binding | 93.1% (99.1% recovery) | 8 h, 37°C |
| A-B intestinal permeability (10−6 cm·s−1) | 53.6% (122% recovery) | TC7 cells, pH 6.5/7.4 |
| Metabolism study | ||
| Metabolic stability | 14% | 0 and 1 h, pH 7.4, 37°C human liver microsomes |
| CYP1A2 inhibition | −8% | CEC substrate, 10 μM |
| CYP2C9 inhibition | −1% | MFC substrate, 10 μM |
| CYP2C19 inhibition | 26% | CEC substrate, 10 μM |
| CYP2C6 inhibition | −30% | MFC substrate, 10 μM |
| CYP3A4 inhibition | 40% | BCF substrate, 10 μM |
| Toxicity | ||
| hERG, inhibition of tail current, IC50 | 0.55 μM |