Table 2 ADMET prediction of three potent SARS-CoV-2 main protease (6YNQ) inhibitors
Model name | Ligand | ||
|---|---|---|---|
A | B | C | |
Absorption | |||
Water solubility (log mol/L) | − 3.078 | − 2.941 | − 2.898 |
Caco2 permeability (log Papp in 10−6 cm/s) | − 0.637 | − 0.773 | − 0.68 |
Intestinal absorption (human) (% Absorbed) | 51.047 | 30.619 | 35.708 |
Skin permeability (log Kp) | − 2.735 | − 2.735 | − 2.735 |
P-glycoprotein substrate | Yes | Yes | Yes |
P-glycoprotein I inhibitor | No | No | No |
P-glycoprotein II inhibitor | No | No | No |
Distribution | |||
VDss (human) (log L/kg) | 0.624 | 0.061 | 0.332 |
Fraction unbound (human) | 0.224 | 0.207 | 0.22 |
BBB permeability (log BB) | − 1.835 | − 2.139 | − 2.408 |
CNS permeability (log PS) | − 4.382 | − 4.777 | − 4.748 |
Metabolism | |||
CYP2D6 substrate | No | No | No |
CYP3A4 substrate | No | No | No |
CYP1A2 inhibitior | No | No | No |
CYP2C19 inhibitior | No | No | No |
CYP2C9 inhibitior | No | No | No |
CYP2D6 inhibitior | No | No | No |
CYP3A4 inhibitior | No | No | No |
Excretion | |||
Total clearance (log ml/min/kg) | − 0.007 | 0.568 | 0.437 |
Renal OCT2 substrate | No | No | No |
Toxicity | |||
Max. tolerated dose (human) (log mg/kg/day) | 0.933 | 0.754 | 0.618 |
hERG I inhibitor | No | No | No |
hERG II inhibitor | No | No | No |
Oral rat acute toxicity (LD50) (mol/kg) | 2.548 | 2.71 | 2.581 |
Oral rat chronic toxicity (LOAEL) (log mg/KgBB/day) | 3.707 | 4.024 | 5.229 |
Hepatotoxicity | No | No | No |
Skin Sensitization | No | No | No |