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Targeting the water network in cyclin G-associated kinase (GAK) with 4-anilino-quin(az)oline inhibitors

Abstract:
Water networks within kinase inhibitor design and more widely within drug discovery are generally poorly understood. The successful targeting of these networks prospectively has great promise for all facets of inhibitor design, including potency and selectivity for the target. Herein, we describe the design and testing of a targeted library of 4‐anilinoquin(az)olines for use as inhibitors of cyclin G‐associated kinase (GAK). GAK cellular target engagement assays, ATP binding‐site modelling and extensive water mapping provide a clear route to access potent inhibitors for GAK and beyond.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1002/cmdc.202000150

Authors

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Role:
Author
ORCID:
0000-0001-5871-3458
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Structural Genomics Consortium
Role:
Author
ORCID:
0000-0003-1396-8400
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Structural Genomics Consortium
Role:
Author


Publisher:
Wiley
Journal:
ChemMedChem More from this journal
Volume:
15
Issue:
13
Pages:
1200-1215
Publication date:
2020-05-26
Acceptance date:
2020-05-01
DOI:
EISSN:
1860-7187
ISSN:
1860-7179
Pmid:
32358915


Language:
English
Keywords:
Pubs id:
1105052
Local pid:
pubs:1105052
Deposit date:
2021-02-17
ARK identifier:

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