Table 6.
Pharmacokinetic (ADMET) and drug likeliness evaluation of hit virtually screened drugs.
| ADMET properties | Z55287118 | Z18483535 | Z97653013 | Drug likeliness properties | Z55287118 | Z18483535 | Z97653013 |
|---|---|---|---|---|---|---|---|
| Caco-2 permeability | −5.246 | −4.924 | −5.286 | Molecular weight | 356.120 g/mol |
453.080 g/mol |
483.160 g/mol |
| HIA | – | – | – | Num. H-bond acceptors | 5 | 8 | 10 |
| PPB | 100.82% | 98.46% | 107.05% | Num. H-bond donors | 2 | 1 | 0 |
| BBB penetration | – | – | – | Num. rotatable bonds | 4 | 6 | 5 |
| CYP1A2 inhibitor | + | + | – | Number of rings | 4 | 5 | 5 |
| CYP2C19 inhibitor | + | + | – | Number of heteroatoms | 5 | 8 | 11 |
| CYP2 C9 inhibitor | + | + | + | Num. heavy atoms | 18 | 22 | 12 |
| CYP2D6 inhibitor | – | – | – | Formal charge | 0 | 0 | 0 |
| CYP3A4 inhibitor | + | + | + | Number of rigid bonds | 25 | 32 | 32 |
| CL | 2.399 | 1.881 | 4.466 | Flexibility | 0.160 | 0.188 | 0.156 |
| T1/2 | 0.068 | 0.177 | 0.476 | Number of stereocenters | 0 | 0 | 0 |
| Human, oral bioavailability | 0.7857 | 0.5571 | 0.5857 | TPSA | 75.270 | 119.750 | 125.480 |
| Hepatotoxicity | – | – | – | logS | −7.404 | −6.373 | −4.364 |
| Respiratory toxicity | – | – | – | logP | 5.082 | 4.195 | 1.355 |
| AMES toxicity | + | + | – | Lipinski rule | Accepted | Accepted | Accepted |
| Skin sensitization | – | – | – | Pfizer rule | Accepted | Accepted | Accepted |
| Carcinogenicity | – | – | + | GSK rule | Rejected | Rejected | Rejected |
| Eye corrosion | – | – | – | Golden Triangle | Accepted | Accepted | Accepted |
| Eye irritation | – | – | – | PAINS | 1 alert | 1 alert | 0 alert |
Abbreviations: ADMET, absorption, distribution, metabolism, excretion, and toxicity; BBB, blood-brain barrier; CL, clearance rate; HIA, human intestine absorption; PPB, plasma protein binding; TPSA, total polar surface area.