TABLE 3.
Predicted pharmacokinetic and pharmacodynamic properties of phebestin and bestatin
| Parameter | Compound |
||
|---|---|---|---|
| Phebestin | Bestatin | Desired value | |
| mol wt (g/mol) | 441.52 | 308.37 | ≤500 |
| No. H-bond acceptors | 6 | 5 | ≤10 |
| No. H-bond donors | 5 | 4 | ≤5 |
| No. rotatable bond (rotors) | 13 | 9 | ≤10 |
| Topological polar surface area (TPSA, Å2) | 141.75 | 112.65 | ≤140 |
| Log P octanol/water partition coefficient | 0.95 | 0.66 | ≤5 |
| Intestinal absorption (% absorbed) | 31.264 | 35.928 | ≥30% |
| Total clearance (log mL/min/kg) | 0.466 | 0.403 | |
| LD50 oral rat acute toxicity (mol/kg) | 2.512 | 1.942 | |
| Hepatoxicity | Yes | Yes | |
| AMES toxicity (act as a carcinogen) | No | No | |
| Max tolerated dose in human (log mL/min/kg) | −0.123 | 0.239 | ≥0.477 high tolerance |
| Drug likeness | |||
| Lipinski (Pfizer); violation | Yes; 0 | Yes; 0 | |
| Ghose; violation | Yes; 0 | Yes; 0 | |
| Veber (GSK); violation | No; 2: rotors >10, TPSA >140 | Yes; 0 | |
| Egan (Pharmacia); violation | No; 1: TPSA >140 | Yes; 0 | |
| Muegge (Bayer) filter; violation | Yes; 0 | Yes | |
| Abbott Bioavailability Score | 0.55 | 0.55 | |