Table 3 Predicted ADME/pharmacokinetics properties of some designed inhibitors
Some selected designed inhibitors | Referenced drug | ||||||
|---|---|---|---|---|---|---|---|
Properties | Parameters | 39b | 39c | 39f | 39g | 39m | Lumateperone |
Absorption | Water solubility | − 3.761 | − 3.362 | − 3.386 | − 3.483 | − 3.363 | − 4.03 |
Caco2 permeability | 0.999 | 1.25 | 1.013 | 1.011 | 1.02 | 1.175 | |
Intestinal absorption (% Absorbed) | 92.854 | 94.5 | 95.056 | 94.854 | 94.608 | 93.538 | |
Skin Permeability | − 2.747 | − 2.751 | − 2.748 | − 2.748 | − 2.741 | − 2.59 | |
P-glycoprotein II inhibitor | Yes | Yes | Yes | Yes | Yes | Yes | |
Distribution | VDss (human) | 0.912 | 0.726 | 0.902 | 0.935 | 0.915 | 1.404 |
Fraction unbound (human) | 0.241 | 0.251 | 0.238 | 0.225 | 0.237 | 0.071 | |
BBB permeability(log BB) | 0.339 | 0.337 | 0.357 | 0.37 | 0.43 | 0.676 | |
CNS permeability | − 1.451 | − 1.446 | − 1.42 | − 1.406 | − 1.444 | − 1.423 | |
Metabolism | CYP1A2 inhibitor | Yes | Yes | Yes | Yes | Yes | No |
CYP2C19 inhibitor | No | No | No | No | No | No | |
CYP2C9 inhibitor | No | No | No | No | No | No | |
CYP2D6 inhibitor | Yes | Yes | Yes | Yes | Yes | Yes | |
CYP3A4 inhibitor | No | No | No | No | No | Yes | |
Excretion | Total clearance | 1.084 | 1.297 | 1.35 | 1.427 | 1.275 | 1.095 |
Renal OCT2 substrate | Yes | Yes | Yes | Yes | Yes | Yes | |