title: The impact of binding thermodynamics on medicinal chemistry optimizations.
abstract: Ligand binding thermodynamics has been attracted considerable interest in the past decade owing to the recognized relation between binding thermodynamic profile and the physicochemical and druglike properties of compounds. In this review, the relation between optimization strategies and ligand properties is presented based on the structural and thermodynamic analysis of ligand-protein complex formation. The control of the binding thermodynamic profile is beneficial for the balanced affinity and physicochemical properties of drug candidates, and early phase optimization gives more opportunity to this control.
authors.affiliation: Research Center for Natural Sciences, Hungarian Academy of Sciences, 2 Magyar tudósok krt. H-1117 Budapest, Hungary.
authors.forename: György G
authors.initials: GG
authors.lastname: Ferenczy
authors.affiliation: Research Center for Natural Sciences, Hungarian Academy of Sciences, 2 Magyar tudósok krt. H-1117 Budapest, Hungary.
authors.forename: György M
authors.initials: GM
authors.lastname: Keserű
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D053508:Matrix Metalloproteinase 12 / Q000737:chemistry / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D011506:Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D012083:Renin / Q000737:chemistry / Q000378:metabolism; D038501:Tankyrases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D000092502:Renin Inhibitors
chemical_list: D018841:HSP90 Heat-Shock Proteins; D008024:Ligands; D053508:Matrix Metalloproteinase 12; D061965:Matrix Metalloproteinase Inhibitors; D011506:Proteins; D012083:Renin; D038501:Tankyrases; D000092502:Renin Inhibitors