Table 11 List of the predicted ADME/pharmacokinetics properties of the eight common docked inhibitors retrieved from web tool pkCSM60.
Properties | Predicted parameters | 5C | 5A | 5D | 5J | 5I | 5H | 5E | 5F |
|---|---|---|---|---|---|---|---|---|---|
Absorption | Water solubility (mol/L) | − 5.89 | − 2.88 | − 2.96 | − 2.21 | − 3.17 | − 5.06 | − 2.88 | − 3.50 |
Caco2 permeability (pkCSM) | 1.29 | 0.22 | 1.66 | 0.15 | 0.52 | 1.47 | 1.25 | 1.34 | |
Intestinal absorption (% Absorption) | 100 | 94.93 | 96.99 | 74.15 | 95.74 | 95.22 | 97.60 | 93.92 | |
Skin permeability (log Kp) | − 2.73 | − 3.30 | − 2.28 | − 3.53 | − 3.50 | − 2.31 | − 2.51 | − 2.95 | |
P-glycoprotein II inhibitor | Yes | No | No | No | No | No | No | No | |
Higher water solubility is preferable for better absorption, Caco-2 > 0.90 (good permeability), % absorption > 80%, skin permeability < − 2.5 | |||||||||
Distribution | BBB permeability (log BB) | 0.16 | − 0.38 | 0.27 | − 0.01 | − 0.44 | 0.27 | 0.35 | − 0.11 |
CNS permeability (log PS) | − 1.49 | − 2.58 | − 2.14 | − 2.51 | − 2.93 | − 1.33 | − 2.03 | − 2.79 | |
log BB > − 1 (good BBB penetration), log PS > − 3 (penetrate the central nervous system (CNS), < − 3 (unable to penetrate the CNS) | |||||||||
Metabolism | CYP2D6 inhibitor | No | No | No | No | No | No | No | No |
CYP2C19 inhibitor | Yes | No | No | No | No | Yes | No | No | |
CYP2C9 inhibitor | Yes | No | No | No | No | Yes | No | No | |
CYP3A4 inhibitor | Yes | No | No | No | No | Yes | No | No | |
CYP2D6 prediction: no | |||||||||
Excretion | Total clearance | 0.56 | 0.44 | 0.73 | 0.47 | 0.73 | 0.01 | 0.67 | 0.07 |
Renal OCT2 substrate | No | No | No | No | No | No | No | No | |
Moderate range of clearance is acceptable, Renal OCT2 substrate: no | |||||||||
Toxicity | AMES toxicity | Yes | No | No | No | No | No | No | Yes |
hERG I inhibitor | No | No | No | No | No | No | No | No | |
Hepatotoxicity | Yes | No | No | No | No | Yes | No | No | |
Skin sensitization | No | No | No | No | No | No | Yes | No | |
