Utilizing comprehensive and mini-kinome panels to optimize the selectivity of quinoline inhibitors for cyclin G associated kinase (GAK)

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:29

Article

Asquith, Christopher R. M.^1,2  Treiber, Daniel K.³  Zuercher, William J.^2,4 

[1] Univ North Carolina Chapel Hill, Dept Pharmacol, Sch Med, Chapel Hill, NC 27599 USA

[2] Univ North Carolina Chapel Hill, Struct Genom Consortium, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA

[3] Eurofins DiscoverX, 42501 Albrae St, Fremont, CA 94538 USA

[4] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

关键词: Cyclin G associated kinase (GAK);    4-anilinoquinoline;    4-Anilinoquinazoline;    Kinome selectivity;    Mini-kinome panel;   

DOI  :  10.1016/j.bmcl.2019.05.025

来源: Elsevier

【 摘 要 】

We demonstrate an innovative approach for optimization of kinase inhibitor potency and selectivity utilising kinase mini-panels and kinome-wide panels. We present a focused case study on development of a selective inhibitor of cyclin G associated kinase (GAK) using the quin(az)oline inhibitor chemotype. These results exemplify a versatile, efficient approach to drive kinome selectivity during inhibitor development programs.

【 授权许可】

Free