Table 1. In Vitro Characterization of Compounds 64, 77, and 78, in Comparison to 1(9)a.
| 64 | 77 | 78 | 1 | |
|---|---|---|---|---|
| KD, ITC (nM) | 68 ± 18 | 29 ± 15 | 29 ± 10 | 3700 ± 800 |
| LogD7.4 | <−1.5 | <−1.4 | <−0.8 | 0.43 ± 0.05 |
| solubilityb (μM) | >850 | 965 ± 38 | >1000 | 805 ± 106 |
| Papp ABc (×10–6 cm/s) | 0.16 ± 0.01 | 0.19 ± 0.12 | 0.18 ± 0.10 | 0.19 ± 0.07 |
| ERd | 1.19 ± 0,15 | 0.84 ± 0.23 | 0.84 ± 0.26 | 52.2 ± 28.0 |
| Clint, human mics. (μL/min/mg) | <3.0 | <3.0 | <3.0 | 36.5 ± 2.5 |
| Nrf2 translocatione (% induction) | 16 ± 2 | 38 ± 0.4 | 37 ± 4 |
a
The values for KD, LogD7.4, solubility, cell permeability, efflux ratio, and the clearance in human liver microsomes and rat hepatocytes are mean values ±standard deviation from ≥three replicates. The induction of Nrf2 translocation into the nucleus is the mean from two measurements on two distinct samples.
b
Solubility in phosphate-buffered saline at 25 °C and pH 7.4.
c
Permeability across a Caco-2 cell monolayer in the apical-to-basolateral direction.
d
ER = efflux ratio (BA/AB) for permeability across a Caco-2 cell monolayer.
e
Induction of Nrf2 translocation into the nucleus at 256 μM.