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

Targeting the water network in cyclin G associated kinase (GAK) with 4-anilino-quin(az)oline inhibitors.
ChemMedChem. 2020 May 01;:
Authors: Asquith CRM, Tizzard GJ, Bennett JM, Wells CI, Elkins JM, Willson TM, Poso A, Laitinen T
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 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.
PMID: 32358915 [PubMed - as supplied by publisher]

Source: ChemMedChem - April 30, 2020 Category: Chemistry Authors: Asquith CRM, Tizzard GJ, Bennett JM, Wells CI, Elkins JM, Willson TM, Poso A, Laitinen T Tags: ChemMedChem Source Type: research