title: The use of thermodynamic and kinetic data in drug discovery: decisive insight or increasing the puzzlement?
abstract: The prime property to rate the success of hit-to-lead-to-drug optimization in drug discovery is binding affinity. Rational approaches try to relate this property with structure. Affinity can be linked to the thermodynamic property, Gibbs free energy of binding, which itself factorizes into enthalpy and entropy. With respect to kinetic properties, affinity can be associated with the ratio of koff and kon of complex formation. Do these features help to obtain better insight into affinity? The present viewpoint assesses our current understanding of thermodynamics- or kinetics-structure relationships and questions the accuracy of data collected to learn about the thermodynamic and kinetic basis to comprehend affinity.
authors.affiliation: Institute of Pharmaceutical Chemistry, University of Marburg, Marbacher Weg 6, 35032 Marburg (Germany).
authors.forename: Gerhard
authors.initials: G
authors.lastname: Klebe
mesh_terms: D002151:Calorimetry; D055808:Drug Discovery; D007700:Kinetics; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D004364:Pharmaceutical Preparations
keywords: affinity; binding kinetics; drug discovery; ligand optimization; thermodynamics