Ligand efficiency and lead optimization.
- Author:
Zong-Ru GUO
- Publication Type:Journal Article
- MeSH:
Drug Design;
Drug Discovery;
methods;
Ligands;
Molecular Structure;
Pharmaceutical Preparations;
chemical synthesis;
chemistry;
Pharmacokinetics;
Pharmacology;
Protein Binding;
Receptors, Drug;
chemistry;
Structure-Activity Relationship;
Thermodynamics
- From:
Acta Pharmaceutica Sinica
2013;48(12):1755-1762
- CountryChina
- Language:Chinese
-
Abstract:
Pharmacological activity and druggability are two pivotal factors in drug innovation, which are respectively determined by the microscopic structure and macroscopic property of a molecule. Since structural optimization consists in a molecular operation in the space with multi-dimensions, and there exists a body of uncertainties for transduction from in vitro activity into in vivo pharmacological response. It is necessary for early stage in lead optimization to evaluate compound quality or efficiency using a kind of metrics containing multi-parameters. On the basis of the describing parameters of activity and druggability, this overview deals with the roles of thermodynamic signatures and binding kinetics of drug-receptor interactions in optimizing quality of compounds, signifying the significance in optimization of microscopic structures for drug discovery.
