Affiliation:
1. Institute of Chemistry, University of Silesia, Szkolna 9, 40-006 Katowice, Poland
2. Computer-Chemie-Centrum, University of Erlangen-Nuernberg, Naegelsbachstrasse 25, 91052 Erlangen, Germany
Abstract
Background:
Potency is the broadest available biological activity data type. In turn,
Ligand Efficiency (LE) is a molecular descriptor that probes the ratio of potency vs Heavy Atom
Count (HAC), which emphasizes low HAC more than potency and thus has drawbacks as an estimator
of drug candidates. The objective was to design a novel transform to probe potency and HAC
interaction in which potency and HAC would be balanced more evenly.
Methods:
In this study, potency data of ChEMBL, PubChem, FDA approvals and drug (fragments)
were analysed. A novel descriptor, a product of the pAC50 value with HAC, multiplicative or Product
Ligand Efficiency (PLE) was designed and tested.
Results:
In particular PLE was compared with pAC50 and LE vs the HAC statistics for different
series of ligands. This indicated that PLE is an informative estimator that can be used to recognize
the potential of drugs. PLE has a maximum value in the range around 30-50 HAC.
Conclusion:
Drug design is a complex problem. Similarly, to drug-likeness, LE prefers small molecules.
This makes LE a tool serendipitously improving drug likeness. In this context, LE performs
unexpectedly well even despite the uncertainty of its physical meaning. PLE is a more evenly balanced
estimator whose physical meaning is the Minimum Inhibitory Concentration (MIC).
Funder
National Centre for Research and Development
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmaceutical Science,Molecular Medicine
Cited by
4 articles.
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