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

doi:10.1021/jm301603n

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 journal › Article › peer-review

15 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 language	English
Pages (from-to)	2155-2159
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	56
Issue number	5
DOIs	https://doi.org/10.1021/jm301603n
Publication status	Published - Mar 14 2013
Externally published	Yes

All Science Journal Classification (ASJC) codes

Molecular Medicine
Drug Discovery

Access to Document

10.1021/jm301603n

Cite this

@article{49a7eb84dc734675807d1841b5964823,

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.",

author = "Akihiro Kobe and Caaveiro, {Jose M.M.} and Shinya Tashiro and Daisuke Kajihara and Masato Kikkawa and Tomoya Mitani and Kouhei Tsumoto",

year = "2013",

month = mar,

day = "14",

doi = "10.1021/jm301603n",

language = "English",

volume = "56",

pages = "2155--2159",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "5",

}

TY - JOUR

T1 - Incorporation of rapid thermodynamic data in fragment-based drug discovery

AU - Kobe, Akihiro

AU - Caaveiro, Jose M.M.

AU - Tashiro, Shinya

AU - Kajihara, Daisuke

AU - Kikkawa, Masato

AU - Mitani, Tomoya

AU - Tsumoto, Kouhei

PY - 2013/3/14

Y1 - 2013/3/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84875144855&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875144855&partnerID=8YFLogxK

U2 - 10.1021/jm301603n

DO - 10.1021/jm301603n

M3 - Article

C2 - 23419007

AN - SCOPUS:84875144855

SN - 0022-2623

VL - 56

SP - 2155

EP - 2159

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 5

ER -

Incorporation of rapid thermodynamic data in fragment-based drug discovery

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this