title: Incorporation of rapid thermodynamic data in fragment-based drug discovery.
abstract: Fragment-based drug discovery (FBDD) has enjoyed increasing popularity in recent years. We introduce SITE (single-injection thermal extinction), a novel thermodynamic methodology that selects high-quality hits early in FBDD. SITE is a fast calorimetric competitive assay suitable for automation that captures the essence of isothermal titration calorimetry but using significantly fewer resources. We describe the principles of SITE and identify a novel family of fragment inhibitors of the enzyme ketosteroid isomerase displaying high values of enthalpic efficiency.
authors: Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors: Akihiro
authors: A
authors: Kobe
authors: Jose M M
authors: JM
authors: Caaveiro
authors: Shinya
authors: S
authors: Tashiro
authors: Daisuke
authors: D
authors: Kajihara
authors: Masato
authors: M
authors: Kikkawa
authors: Tomoya
authors: T
authors: Mitani
authors: Kouhei
authors: K
authors: Tsumoto
mesh_terms: D002151:Calorimetry / Q000379:methods; D055808:Drug Discovery / Q000379:methods*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000302:isolation & purification; D054852:Small Molecule Libraries; D013251:Steroid Isomerases / Q000037:antagonists & inhibitors*; D020349:Surface Plasmon Resonance; D013816:Thermodynamics
chemical_list: D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; D013251:Steroid Isomerases; C022660:steroid delta-isomerase