Incorporation of rapid thermodynamic data in fragment-based drug discovery.

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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

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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