Table 4.
ADMET prediction results
| Type | Properties | Values |
|---|---|---|
| Absorption | Water solubility (log mol/L) | −2.892 |
| Caco-2 permeability (log Papp in 10 cm/s) | −1.874 | |
| Intestinal absorption (human) (% Absorbed) | 0 | |
| Skin Permeability (log Kp) | −2.735 | |
| P-glycoprotein substrate | Yes | |
| P-glycoprotein I inhibitor | No | |
| P-glycoprotein II inhibitor | No | |
| Distribution | VDss (human) (log L/kg) | −0.274 |
| Fraction unbound (human) | 0.34 | |
| BBB permeability (log BB) | −3.923 | |
| CNS permeability (log PS) | −6.421 | |
| Metabolism | CYP2D6 substrate | No |
| CYP3A4 substrate | Yes | |
| CYP1A2 inhibitor | No | |
| CYP2C19 inhibitor | No | |
| CYP2C9 inhibitor | No | |
| CYP2D6 inhibitor | No | |
| CYP3A4 inhibitor | No | |
| Excretion | Total Clearance (log ml/min/kg) | −2.059 |
| Renal OCT2 substrate | No | |
| Toxicity | AMES toxicity | No |
| Max. tolerated dose (human) (log mg/kg/day) | 0.438 | |
| hERG I inhibitor | No | |
| hERG II inhibitor | No | |
| Oral Rat Acute Toxicity (LD50) (mol/kg) | 2.482 | |
| Oral Rat Chronic Toxicity (LOAEL) (log mg/kg_bw/day) | 11.816 | |
| Hepatotoxicity | No | |
| Skin Sensitisation | No | |
| T. Pyriformis toxicity (log ug/L) | 0.285 | |
| Minnow toxicity (log mM) | 12.298 |
Based on pkCSM ADMET predictive model [32], a compound is said to have high Caco-2 permeability at a value of >0.90; poor GIA at less than 30% absorption; low skin permeability (logKp > −2.5); VDss is low at < 0.71 L/kg (log VDss < −0.15) and high at > 2.81 L/kg (log VDss > 0.45); BBB permeant at a logBB > 0.33 and non-permeant at logBB < −1; CNS permeant at a logPS > −2 and non permenat at a logPS < −3; Tetrahymena pyriformis toxicity (pIGC50) at a value > − 0.5 log µg/L is considered toxic; minnow toxicity (LC50) at a value < 0.5 mM (logLC50 < −0.3) is regarded as high acute toxicity; maximum recommended tolerated doses (MRTD) of ≤ 0.477 log(mg/kg/day) is considered low, and high if >0.477 log(mg/kg/day)