Incorporation of rapid thermodynamic data in fragment-based drug discovery.
Article Details
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Kobe A, Caaveiro JM, Tashiro S, Kajihara D, Kikkawa M, Mitani T, Tsumoto K
Incorporation of rapid thermodynamic data in fragment-based drug discovery.
J Med Chem. 2013 Mar 14;56(5):2155-9. doi: 10.1021/jm301603n. Epub 2013 Feb 27.
- PubMed ID
- 23419007 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) 5-(2-PHENYLPYRAZOLO[1,5-A]PYRIDIN-3-YL)-1H-PYRAZOLO[3,4-C]PYRIDAZIN-3-AMINE Mitogen-activated protein kinase 1 Kd (nM) 850 N/A N/A Details Deoxycholic acid Steroid Delta-isomerase Kd (nM) 16000 N/A N/A Details