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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TY - JOUR

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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