TAK1 inhibition in the DFG-out conformation

Iain Kilty; Martin P. Green; Andrew S. Bell; David G. Brown; Peter G. Dodd; Christopher Hewson; Samantha J. Hughes; Christopher Phillips; Thomas Ryckmans; Robert T. Smith; Willem P. van Hoorn; Philip Cohen; Lyn H. Jones

doi:10.1111/cbdd.12169

TAK1 inhibition in the DFG-out conformation

Iain Kilty, Martin P. Green, Andrew S. Bell, David G. Brown, Peter G. Dodd, Christopher Hewson, Samantha J. Hughes, Christopher Phillips, Thomas Ryckmans, Robert T. Smith, Willem P. van Hoorn, Philip Cohen, Lyn H. Jones (Lead / Corresponding author)

Biological Chemistry and Drug Discovery

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

The first example of an inhibitor of the kinase TAK1 that binds in the DFG-out conformation is disclosed. These preliminary studies used kinase-targeted screening and structure-based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell-based, anti-inflammatory assay. The first example of an inhibitor of the kinase TAK1 that binds in the DFG-out conformation is disclosed. These preliminary studies used kinase-targeted screening and structure-based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell-based, anti-inflammatory assay.

Original language	English
Pages (from-to)	500-505
Number of pages	6
Journal	Chemical Biology and Drug Design
Volume	82
Issue number	5
Early online date	16 Oct 2013
DOIs	https://doi.org/10.1111/cbdd.12169
Publication status	Published - 1 Nov 2013

Keywords

Chemical biology
Drug design
Kinase
Phosphatase
Structure-based drug design
X-ray crystallography

ASJC Scopus subject areas

Biochemistry
Molecular Medicine

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10.1111/cbdd.12169

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title = "TAK1 inhibition in the DFG-out conformation",

abstract = "The first example of an inhibitor of the kinase TAK1 that binds in the DFG-out conformation is disclosed. These preliminary studies used kinase-targeted screening and structure-based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell-based, anti-inflammatory assay. The first example of an inhibitor of the kinase TAK1 that binds in the DFG-out conformation is disclosed. These preliminary studies used kinase-targeted screening and structure-based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell-based, anti-inflammatory assay.",

keywords = "Chemical biology, Drug design, Kinase, Phosphatase, Structure-based drug design, X-ray crystallography",

author = "Iain Kilty and Green, \{Martin P.\} and Bell, \{Andrew S.\} and Brown, \{David G.\} and Dodd, \{Peter G.\} and Christopher Hewson and Hughes, \{Samantha J.\} and Christopher Phillips and Thomas Ryckmans and Smith, \{Robert T.\} and \{van Hoorn\}, \{Willem P.\} and Philip Cohen and Jones, \{Lyn H.\}",

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doi = "10.1111/cbdd.12169",

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T1 - TAK1 inhibition in the DFG-out conformation

AU - Kilty, Iain

AU - Green, Martin P.

AU - Bell, Andrew S.

AU - Brown, David G.

AU - Dodd, Peter G.

AU - Hewson, Christopher

AU - Hughes, Samantha J.

AU - Phillips, Christopher

AU - Ryckmans, Thomas

AU - Smith, Robert T.

AU - van Hoorn, Willem P.

AU - Cohen, Philip

AU - Jones, Lyn H.

PY - 2013/11/1

Y1 - 2013/11/1

N2 - The first example of an inhibitor of the kinase TAK1 that binds in the DFG-out conformation is disclosed. These preliminary studies used kinase-targeted screening and structure-based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell-based, anti-inflammatory assay. The first example of an inhibitor of the kinase TAK1 that binds in the DFG-out conformation is disclosed. These preliminary studies used kinase-targeted screening and structure-based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell-based, anti-inflammatory assay.

AB - The first example of an inhibitor of the kinase TAK1 that binds in the DFG-out conformation is disclosed. These preliminary studies used kinase-targeted screening and structure-based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell-based, anti-inflammatory assay. The first example of an inhibitor of the kinase TAK1 that binds in the DFG-out conformation is disclosed. These preliminary studies used kinase-targeted screening and structure-based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell-based, anti-inflammatory assay.

KW - Chemical biology

KW - Drug design

KW - Kinase

KW - Phosphatase

KW - Structure-based drug design

KW - X-ray crystallography

UR - https://www.scopus.com/pages/publications/84885740180

U2 - 10.1111/cbdd.12169

DO - 10.1111/cbdd.12169

M3 - Article

C2 - 23745990

AN - SCOPUS:84885740180

SN - 1747-0277

VL - 82

SP - 500

EP - 505

JO - Chemical Biology and Drug Design

JF - Chemical Biology and Drug Design

IS - 5

ER -

TAK1 inhibition in the DFG-out conformation

Abstract

Keywords

ASJC Scopus subject areas

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