RT Journal Article
SR Electronic
T1 Targeting the water network in cyclin G associated kinase (GAK) with 4-anilino-quin(az)oline inhibitors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.06.976563
DO 10.1101/2020.03.06.976563
A1 Asquith, Christopher R. M.
A1 Tizzard, Graham J.
A1 Bennett, James M.
A1 Wells, Carrow I.
A1 Elkins, Jonathan M.
A1 Willson, Timothy M.
A1 Poso, Antti
A1 Laitinen, Tuomo
YR 2020
UL http://biorxiv.org/content/early/2020/03/07/2020.03.06.976563.abstract
AB 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 on target. Here we describe the design and testing of a targeted library of 4-anilinoquinolines for use as inhibitors of cyclin G associated kinase (GAK). The 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.