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Pharmaceutical research skill covering bioactive compound search (ChEMBL), drug-likeness screening (Lipinski Ro5 + Veber via PubChem), drug-drug interaction lookups (OpenFDA), gene-disease associations (OpenTargets GraphQL), and ADMET reasoning guidance. All free public APIs, zero auth, stdlib-only Python. Includes helper scripts for batch Ro5 screening and target-to-compound pipelines. Moved to optional-skills/research/ (niche domain skill, not built-in). Fixed: authors→author frontmatter, removed unused jq prerequisite, bare except→except Exception. Co-authored-by: bennytimz <oluwadareab12@gmail.com> Salvaged from PR #8695.
1.9 KiB
1.9 KiB
ADMET Reference Guide
Comprehensive reference for Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis in drug discovery.
Drug-Likeness Rule Sets
Lipinski's Rule of Five (Ro5)
| Property | Threshold |
|---|---|
| Molecular Weight (MW) | ≤ 500 Da |
| Lipophilicity (LogP) | ≤ 5 |
| H-Bond Donors (HBD) | ≤ 5 |
| H-Bond Acceptors (HBA) | ≤ 10 |
Reference: Lipinski et al., Adv. Drug Deliv. Rev. 23, 3–25 (1997).
Veber's Oral Bioavailability Rules
| Property | Threshold |
|---|---|
| TPSA | ≤ 140 Ų |
| Rotatable Bonds | ≤ 10 |
Reference: Veber et al., J. Med. Chem. 45, 2615–2623 (2002).
CNS Penetration (BBB)
| Property | CNS-Optimal |
|---|---|
| MW | ≤ 400 Da |
| LogP | 1–3 |
| TPSA | < 90 Ų |
| HBD | ≤ 3 |
CYP450 Metabolism
| Isoform | % Drugs | Notable inhibitors |
|---|---|---|
| CYP3A4 | ~50% | Grapefruit, ketoconazole |
| CYP2D6 | ~25% | Fluoxetine, paroxetine |
| CYP2C9 | ~15% | Fluconazole, amiodarone |
| CYP2C19 | ~10% | Omeprazole, fluoxetine |
| CYP1A2 | ~5% | Fluvoxamine, ciprofloxacin |
hERG Cardiac Toxicity Risk
Structural alerts: basic nitrogen (pKa 7–9) + aromatic ring + hydrophobic moiety, LogP > 3.5 + basic amine.
Mitigation: reduce basicity, introduce polar groups, break planarity.
Common Bioisosteric Replacements
| Original | Bioisostere | Purpose |
|---|---|---|
| -COOH | -tetrazole, -SO₂NH₂ | Improve permeability |
| -OH (phenol) | -F, -CN | Reduce glucuronidation |
| Phenyl | Pyridine, thiophene | Reduce LogP |
| Ester | -CONHR | Reduce hydrolysis |
Key APIs
- ChEMBL: https://www.ebi.ac.uk/chembl/api/data/
- PubChem: https://pubchem.ncbi.nlm.nih.gov/rest/pug/
- OpenFDA: https://api.fda.gov/drug/
- OpenTargets GraphQL: https://api.platform.opentargets.org/api/v4/graphql