Table 8.
Important computed ADMET properties and their recommended ranges for orally active drugs
| Property | Description | Recommended range | FC101a | FC101 Oxazole | FC101 Imidazole | FC101 Phos |
|---|---|---|---|---|---|---|
| MW | Molecular weight in Da | <450 | 292.34 | 300.32 | 299.33 | 372.32 |
| PSA | Surface sum of all polar atoms and attached atoms in Å2 | <140 | 110.708 | 89.708 | 94.106 | 167.62 |
| Nrot | Number of rotatable bonds | <10 | 4 | 3 | 3 | 6 |
| HBD | Number of hydrogen bond donors | <5 | 3a | 1 | 2 | 4 |
| HBA | Number of hydrogen bond acceptors | ≤8 | 6 | 6 | 6 | 9 |
| LogP | Octanol-water partition coefficient | ≤4.5 | 0.89 | 2.35 | 2.14 | −0.91 |
| LogD | Octanol-water distribution coefficient | ≤3.5 | −0.53 | 2.35 | 2.11 | −0.9 |
| Sw | Aqueous solubility in mg/ml | ≥0.010 | 2.34 | 0.0261 | 0.0259 | 0.7740 |
| LogS | Log of aqueous solubility | −6.0 – 0.5 | −3.39 | −4.29 | −3.66 | −1.81 |
| MDCK | Apparent Madin-Darby canine kidney cell permeability in cm/s × 107 | ≥30 | 44.79a | 313.79 | 212.86 | 14.82 |
| Peff | Human effective jejunal permeation in cm/s × 104 | ≥0.5 | 0.75a | 3.29 | 2.36 | 0.29 |
| Fsp3 | Fraction of sp3 C to total C atoms | >0.36 | 0.467 | 0.313 | 0.313 | 0.467 |
| RBP | Blood-to-plasma concentration ratio | <1.0 | 0.97a | 0.81 | 0.85 | 0.62 |
| Vd | Volume of distribution in L/kg | ≤3.7 | 6.7 | 2.76 | 3.82 | 0.6 |
| Fup | Percent of drug unbound to plasma proteins | >10 % | 66.61 | 13.1 | 15.35 | 36.48 |
| MolVol | Molal volume at normal boiling point in cm3/mol | <475 | 308 | 294 | 301 | 364 |
| hERG | pIC50 as measure of affinity for hERG K+ channel | ≤5.5 | 4.51 | 4.24 | 4.53 | 3.76 |
| MRTD | Maximum recommended therapeutic dose in mg/kg/day | >3.16 | >3.16 | >3.16 | <3.16 | <3.16 |
| TOX | Risk summary for mutagenic potential in S. typhimurium | ≤1 | 1a | 0 | 0 | 0 |
| MUT | ||||||
| Risk | ||||||
| Absn_Risk | Risk summary for oral absorption | <3.5 | 0.99 | 0 | 0 | 3.5 |
| ADMET_Risk | Summary of all predicted ADMET risk factors | ≤6.5 | 1.99 | 0 | 0.06 | 3.5 |
Recommended ranges are determined by range of 95 % of orally bioactive drugs and/or cut-offs pre-determined by ADMET Predictor Version 2.0, as defined below. Seven of the cut-offs are within the range of 95 % of orally bioactive drugs. Molar weight (range for 95 % of drugs: 130–725 Da); LogP (range for 95 % of drugs: −2 to 6.5); HBA (range for 95 % of drugs: 2–20); HBD (range for 95 % of drugs: 0–6); nrot (range for 95 % of drugs: 0–15); MDCK permeability in nm/s (range for 95 % of drugs: < 5 low, > 500 high); LogS (range for 95 % of drugs: −6.0 to 0.5) (Ntie-Kang et al. 2013); TOX_MUT_Risk, Absn_Risk, ADMET_Risk, Sw, Peff, MDCK, MW, Mol Vol, LogD, Vd, Fup, and hERG pIC50 exact cut-offs pre-determined by ADMET Predictor. (ADMET Predictor V2 Manual); PSA (<140 based on Veber et al. (2002)); Fsp3 range based on Lovering et al. (2009). Bolded values indicate values outside the range of 95 % of orally bioactive drugs and/or exceeding risk cut-off. aValues indicate properties likely needing optimization or in-vitro assessment