ADMET
The ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties of a molecule provide essential insights into its drug-likeness, bioavailability, and safety profile. These properties influence how well a compound is absorbed, distributed in the body, metabolized, excreted, and whether it has toxic effects. Below are the key ADMET parameters used in evaluating molecular candidates:
| Parameter | Description | Classification / Ranges | Example Value |
|---|---|---|---|
| Lipophilicity, logP | LogP measures a compound’s lipophilicity by quantifying its distribution between octanol and water | Optimal: [0; 3], Bad: (3; +∞) | 1.13 |
| Solubility, logS | LogS, where S is the aqueous solubility in mol/L | Soluble: (−2; +∞) Slightly soluble: [−4; −2] Insoluble: (−∞; −4) | −2.97 |
| Caco-2 (Cell Effective Permeability), logPapp | The apparent permeability coefficient (Papp) is calculated from the permeation rate and compound concentration at t=0h and t=2h within Caco-2 cells (human colon epithelial cancer cell line) | High: (−5; +∞) Moderate: [−6; −5] Low: (−∞; −6) | −4.66 |
| PAMPA Permeability, classification | Parallel artificial membrane permeability assay (PAMPA). Compounds which have a Papp < 10 × 10−6cm/s are classified as low permeability and compounds with a Papp > 10 × 10−6cm/s are classified as high permeability | The prediction probability values are transformed into six symbols: 0–0.1 (−−), 0.1–0.3 (−), 0.3–0.5 (∼), 0.5–0.7 (+), 0.7–0.9 (++), 0.9–1.0 (+++) | +++ |
| Pgp (P-glycoprotein) Inhibition, classification | P-glycoprotein (P-gp) molecules are widely distributed across various organs, including the blood-brain barrier (BBB), kidney proximal tubules, and bile ductules. Inhibiting P-gp can enhance the absorption, distribution, metabolism, and elimination processes of its substrates, potentially improving their overall pharmacokinetic profile | The prediction probability values are transformed into six symbols: 0–0.1 (−−), 0.1–0.3 (−), 0.3–0.5 (∼), 0.5–0.7 (+), 0.7–0.9 (++), 0.9–1.0 (+++) | --- |
| BBB (Blood-Brain Barrier Penetration), classification | Molecules are divided into BBB+ and BBB− classes if logBB ≥ −1 and logBB < −1. BBB+ is acceptable only for CNS drugs, for other drugs it is a negative label | The prediction probability values are transformed into six symbols: 0–0.1 (−−), 0.1–0.3 (−), 0.3–0.5 (∼), 0.5–0.7 (+), 0.7–0.9 (++), 0.9–1.0 (+++) | ++ |
| PPBR (Plasma Protein Binding Rate) % | The less bound a drug is, the more efficiently it can traverse and diffuse to the site of actions | Optimal: [0, 90) Bad: [90, 100] | 68.89 |
| TPSA (Ų) | Surface belonging to polar atoms, is a descriptor that was shown to correlate well with passive molecular transport through membranes | Optimal: [0, 140] | 95.17 |
| HBD | Number of H-bond donors | Optimal: [0, 7] | 1 |
| HBA | Number of H-bond acceptors | Optimal: [0, 12] | 6 |
| MCE-18 | Medicinal Chemistry Evolution measure to effectively score molecules by novelty in terms of their cumulative sp3 complexity | Good: (100, +∞) Medium: [65; 100] Bad: [0; 65] | 15.41 |