Towards holistic Compound Quality Scores: Extending ligand efficiency indices with compound pharmacokinetic characteristics.
Drug Discov Today
; 28(11): 103758, 2023 Nov.
Article
in En
| MEDLINE
| ID: mdl-37660984
ABSTRACT
The suitability of small molecules as oral drugs is often assessed by simple physicochemical rules, the application of ligand efficiency scores or by composite scores based on physicochemical compound properties. These rules and scores are empirical and typically lack mechanistic background, such as information on pharmacokinetics (PK). We introduce new types of Compound Quality Scores (CQS, specifically called dose scores and cmax scores), which explicitly include predicted or, when available, experimental PK parameters and combine these with on-target potency. These CQS scores are surrogates for an estimated dose and corresponding cmax and allow prioritizing of compounds within test cascades as well as before synthesis. We demonstrate the complementarity and, in most cases, superior performance relative to existing efficiency metrics by project examples.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Benchmarking
Type of study:
Prognostic_studies
Language:
En
Journal:
Drug Discov Today
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2023
Document type:
Article