Incorporation of rapid thermodynamic data in fragment-based drug discovery

Akihiro Kobe, Jose M.M. Caaveiro, Shinya Tashiro, Daisuke Kajihara, Masato Kikkawa, Tomoya Mitani, Kouhei Tsumoto

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2155-2159
Number of pages5
JournalJournal of Medicinal Chemistry
Volume56
Issue number5
DOIs
Publication statusPublished - Mar 14 2013
Externally publishedYes

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Drug Discovery
Thermodynamics
Hot Temperature
Injections
Ketosteroids
Isomerases
Calorimetry
Automation
Enzyme Inhibitors

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Kobe, A., Caaveiro, J. M. M., Tashiro, S., Kajihara, D., Kikkawa, M., Mitani, T., & Tsumoto, K. (2013). Incorporation of rapid thermodynamic data in fragment-based drug discovery. Journal of Medicinal Chemistry, 56(5), 2155-2159. https://doi.org/10.1021/jm301603n

Incorporation of rapid thermodynamic data in fragment-based drug discovery. / Kobe, Akihiro; Caaveiro, Jose M.M.; Tashiro, Shinya; Kajihara, Daisuke; Kikkawa, Masato; Mitani, Tomoya; Tsumoto, Kouhei.

In: Journal of Medicinal Chemistry, Vol. 56, No. 5, 14.03.2013, p. 2155-2159.

Research output: Contribution to journalArticle

Kobe, A, Caaveiro, JMM, Tashiro, S, Kajihara, D, Kikkawa, M, Mitani, T & Tsumoto, K 2013, 'Incorporation of rapid thermodynamic data in fragment-based drug discovery', Journal of Medicinal Chemistry, vol. 56, no. 5, pp. 2155-2159. https://doi.org/10.1021/jm301603n
Kobe, Akihiro ; Caaveiro, Jose M.M. ; Tashiro, Shinya ; Kajihara, Daisuke ; Kikkawa, Masato ; Mitani, Tomoya ; Tsumoto, Kouhei. / Incorporation of rapid thermodynamic data in fragment-based drug discovery. In: Journal of Medicinal Chemistry. 2013 ; Vol. 56, No. 5. pp. 2155-2159.
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