Pseudokinase drug intervention: a potentially poisoned chalice

Jeroen Claus; Angus J. M. Cameron; Peter Parker

doi:10.1042/BST20130078

Pseudokinase drug intervention: a potentially poisoned chalice

Jeroen Claus^*, Angus J. M. Cameron, Peter Parker

^*Corresponding author for this work

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

12 Citations (Scopus)

Abstract

Pseudokinases, the catalytically impaired component of the kinome, have recently been found to share more properties with active kinases than previously thought. In many pseudokinases, ATP binding and even some activity is preserved, highlighting these proteins as potential drug targets. In both active kinases and pseudokinases, binding of ATP or drugs in the nucleotide-binding pocket can stabilize specific conformations required for activity and protein-protein interactions. We discuss the implications of locking particular conformations in a selection of (pseudo)kinases and the dual potential impact on the druggability of these proteins.

Original language	English
Pages (from-to)	1083-1088
Number of pages	6
Journal	Biochemical Society Transactions
Volume	41
Issue number	4
DOIs	https://doi.org/10.1042/BST20130078
Publication status	Published - Aug 2013

Keywords

cancer
epidermal growth factor receptor (EGFR)
kinase
kinase inhibitor
protein kinase A (PKA)
pseudokinase
GROWTH-FACTOR RECEPTOR
PROTEIN-KINASE
ALLOSTERIC MECHANISM
DOMAIN
INHIBITOR
BINDING
CANCER
RAF
BRAF
ACTIVATION

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1042/BST20130078

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title = "Pseudokinase drug intervention: a potentially poisoned chalice",

abstract = "Pseudokinases, the catalytically impaired component of the kinome, have recently been found to share more properties with active kinases than previously thought. In many pseudokinases, ATP binding and even some activity is preserved, highlighting these proteins as potential drug targets. In both active kinases and pseudokinases, binding of ATP or drugs in the nucleotide-binding pocket can stabilize specific conformations required for activity and protein-protein interactions. We discuss the implications of locking particular conformations in a selection of (pseudo)kinases and the dual potential impact on the druggability of these proteins.",

keywords = "cancer, epidermal growth factor receptor (EGFR), kinase, kinase inhibitor, protein kinase A (PKA), pseudokinase, GROWTH-FACTOR RECEPTOR, PROTEIN-KINASE, ALLOSTERIC MECHANISM, DOMAIN, INHIBITOR, BINDING, CANCER, RAF, BRAF, ACTIVATION",

author = "Jeroen Claus and Cameron, {Angus J. M.} and Peter Parker",

year = "2013",

month = aug,

doi = "10.1042/BST20130078",

language = "English",

volume = "41",

pages = "1083--1088",

journal = "Biochemical Society Transactions",

issn = "0300-5127",

publisher = "Portland Press Ltd.",

number = "4",

}

TY - JOUR

T1 - Pseudokinase drug intervention

T2 - a potentially poisoned chalice

AU - Claus, Jeroen

AU - Cameron, Angus J. M.

AU - Parker, Peter

PY - 2013/8

Y1 - 2013/8

N2 - Pseudokinases, the catalytically impaired component of the kinome, have recently been found to share more properties with active kinases than previously thought. In many pseudokinases, ATP binding and even some activity is preserved, highlighting these proteins as potential drug targets. In both active kinases and pseudokinases, binding of ATP or drugs in the nucleotide-binding pocket can stabilize specific conformations required for activity and protein-protein interactions. We discuss the implications of locking particular conformations in a selection of (pseudo)kinases and the dual potential impact on the druggability of these proteins.

AB - Pseudokinases, the catalytically impaired component of the kinome, have recently been found to share more properties with active kinases than previously thought. In many pseudokinases, ATP binding and even some activity is preserved, highlighting these proteins as potential drug targets. In both active kinases and pseudokinases, binding of ATP or drugs in the nucleotide-binding pocket can stabilize specific conformations required for activity and protein-protein interactions. We discuss the implications of locking particular conformations in a selection of (pseudo)kinases and the dual potential impact on the druggability of these proteins.

KW - cancer

KW - epidermal growth factor receptor (EGFR)

KW - kinase

KW - kinase inhibitor

KW - protein kinase A (PKA)

KW - pseudokinase

KW - GROWTH-FACTOR RECEPTOR

KW - PROTEIN-KINASE

KW - ALLOSTERIC MECHANISM

KW - DOMAIN

KW - INHIBITOR

KW - BINDING

KW - CANCER

KW - RAF

KW - BRAF

KW - ACTIVATION

U2 - 10.1042/BST20130078

DO - 10.1042/BST20130078

M3 - Article

SN - 0300-5127

VL - 41

SP - 1083

EP - 1088

JO - Biochemical Society Transactions

JF - Biochemical Society Transactions

IS - 4

ER -

Pseudokinase drug intervention: a potentially poisoned chalice

Abstract

Keywords

UN SDGs

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