Towards holistic Compound Quality Scores: Extending ligand efficiency indices with compound pharmacokinetic...

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 c_max 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 c_max 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.