TABLE 4.
In vitro kinetic solubility, microsomal and plasma stabilities, and plasma protein binding of AD01, PhX6 and DpNEt, n = 3.
| Compound | Predicted solubility µM | Lipophilicity LogD7.4 | Permeability LogPapp | Clint mL/min/kg | Plasma half-life min | Plasma protein binding %, (fu) | |||
|---|---|---|---|---|---|---|---|---|---|
| pH 2 | pH 6.5 | pH 7.4 | Mouse | Human | |||||
| AD01 | >150 | >150 | >150 | 0.2 | −6.4 | 80.6 | 16.2 | 85 | ND* |
| PhX6 | >150 | <5 | <5 | 1.0 | −4.4 | 88.2 | 20.2 | >150 | 90 (0.10) |
| DpNEt | >150 | >150 | >150 | 2.3 | −3.7 | 22.3 | 4.0 | >150 | 94 (0.06) |
ND* = not determined due to plasma instability; Clint, intrinsic liver clearance rate; fu fraction unbound.