Table 3 ADMET properties of potential inhibitors of anti-insulinemic resistance targets
Absorption | |||||||
Intestinal absorption (%) | Water solubility (log mol/L) | Skin Permeability (log Kp) | P-glycoprotein substrate | P-glycoprotein I inhibitor | P-glycoprotein II inhibitor | ||
R | Metformin | 59.40 | −2.657 | −2.74 | Yes | No | No |
1 | d-Lyxo-d-manno-nononic-1,4-lactone | 22.72 | −1.15 | −0.33 | Yes | No | No |
2 | Oleic acid | 91.77 | −5.69 | −2.52 | No | No | No |
3 | Cyclohexane, 1,1′-(2-methyl-1,3 propanediyl)bis | 93.62 | −7.10 | −2.28 | No | No | No |
Distribution | |||||||
VDss (human) (log L/kg) | Fraction unbound (human) | BBB permeability | CNS permeability | ||||
R | Metformin | −0.33 | 0.88 | −0.80 | −4.24 | ||
1 | d-Lyxo-d-manno-nononic-1,4-lactone | −0.03 | 0.85 | −1.3 | −4.31 | ||
2 | Oleic acid | −0.57 | 0.046 | −0.18 | −1.65 | ||
3 | Cyclohexane, 1,1′-(2-methyl-1,3 propanediyl)bis | 0.53 | 0.009 | 0.871 | −1.07 | ||
Metabolism | |||||||
CYP2D6 substrate | CYP3A4 substrate | CYP1A2 inhibitor | CYP2C19 inhibitor | CYP2C9 inhibitor | CYP3A4 inhibitor | ||
R | Metformin | No | No | No | No | No | No |
1 | d-Lyxo-d-manno-nononic-1,4-lactone | No | No | No | No | No | No |
2 | Oleic acid | Yes | Yes | Yes | No | No | No |
3 | Cyclohexane, 1,1′-(2-methyl-1,3 propanediyl)bis | No | Yes | Yes | No | No | No |
Excretion | Toxicity | ||||||
Total Clearance (log ml/min/kg) | Renal OCT2 substrate | Max. tolerated dose (log mg/kg/day) | AMES toxicity | Hepatotoxicity | Skin sensitization | ||
R | Metformin | 0.1 | No | 0.81 | Yes | No | Yes |
1 | d-Lyxo-d-manno-nononic-1,4-lactone | 0.82 | No | 1.92 | No | No | No |
2 | Oleic acid | 1.88 | No | −0.94 | No | Yes | Yes |
3 | Cyclohexane, 1,1′-(2-methyl-1,3 propanediyl)bis | 1.22 | No | −0.51 | No | No | Yes |