Table 4. In Vitro ADMET Profile of 7l.
| test type | 7l | reference cmpd |
|---|---|---|
| aqueous solubilitya | 195.8 μM | |
| bidirectional permeability (Caco-2, pH 6.5/7.4)b | Papp A-B = 44.1 × 10–6 cm/s Papp B-A = 19.4 × 10–6 cm/s | Papp A-B = 26.9 × 10–6 cm/s Papp B-A = 39.7 × 10–6 cm/s (propranolol) |
| microsomal stabilityc (half-life/intrinsic clearance) | t1/2 = 118.9 min Clint = 58.3 μL/(min mg) protein | t1/2 = 88.5 min Clint = 7.8 μL/(min mg) protein (imipramine) |
| CYP2D6 inhibitiond | 2.5 μM | 0.018 μM (quinidine) |
| CYP3A4 inhibitiond | 0.18 μM | 0.046 μM (ketoconazole) |
| potassium channel hERG binding | 5.7e | 78f (terfenadine) |
a
Measured in simulated gastric fluid.
b
Tested concentration of 10 μM.
c
Assessed at a protein concentration of 0.1 mg/mL in the human liver microsome assay.
d
CYP isoform inhibition is expressed as an IC50 value.
e
% inhibition at 1 μM.
f
Ki value in nM.