title: Leveraging the contribution of thermodynamics in drug discovery with the help of fluorescence-based thermal shift assays.
abstract: The development of new drugs with better pharmacological and safety properties mandates the optimization of several parameters. Today, potency is often used as the sole biochemical parameter to identify and select new molecules. Surprisingly, thermodynamics, which is at the core of any interaction, is rarely used in drug discovery, even though it has been suggested that the selection of scaffolds according to thermodynamic criteria may be a valuable strategy. This poor integration of thermodynamics in drug discovery might be due to difficulties in implementing calorimetry experiments despite recent technological progress in this area. In this report, the authors show that fluorescence-based thermal shift assays could be used as prescreening methods to identify compounds with different thermodynamic profiles. This approach allows a reduction in the number of compounds to be tested in calorimetry experiments, thus favoring greater integration of thermodynamics in drug discovery.
authors: Druggability-Enzymology-Profiling Unit, Oncology Research, Novartis Institutes of BioMedical Research, Basel, Switzerland.
authors: Jean Christophe
authors: JC
authors: Hau
authors: Patrizia
authors: P
authors: Fontana
authors: Catherine
authors: C
authors: Zimmermann
authors: Alain
authors: A
authors: De Pover
authors: Dirk
authors: D
authors: Erdmann
authors: Patrick
authors: P
authors: Chène
mesh_terms: D001681:Biological Assay; D002151:Calorimetry; D055808:Drug Discovery; D005453:Fluorescence; D007700:Kinetics; D011485:Protein Binding / Q000502:physiology; D011489:Protein Denaturation; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism; D013696:Temperature; D013816:Thermodynamics
chemical_list: D054852:Small Molecule Libraries; D017526:Receptor, IGF Type 1