Identification and Optimization of 4‐Anilinoquinolines as Inhibitors of Cyclin G Associated Kinase
4-Anilinoquinolines were identified as potent and narrow-spectrum inhibitors of the cyclin G associated kinase (GAK), an important regulator of viral and bacterial entry into host cells. Optimization of the 4-anilino group and the 6,7-quinoline substituents produced GAK inhibitors with nanomolar activity, over 50 000-fold selectivity relative to other members of the numb-associated kinase (NAK) subfamily, and a compound (6,7-dimethoxy-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine; 49) with a narrow-spectrum kinome profile. These compounds may be useful tools to explore the therapeutic potential of GAK in prevention of a broad range of infectious and systemic diseases.
Authors
- Christopher R. M. Asquith (ORCID: https://orcid.org/0000-0001-5871-3458)
- William J. Zuercher (ORCID: https://orcid.org/0000-0002-9836-0068)
- Gary L. Johnson (ORCID: https://orcid.org/0000-0003-2867-0551)
- Jonathan M. Elkins (ORCID: https://orcid.org/0000-0003-2858-8929)
- Paulo H. Godoi (ORCID: https://orcid.org/0000-0003-1859-3513)
- Ronna E. Dornsife (ORCID: https://orcid.org/0000-0002-6562-8486)
- Tuomo Laitinen (ORCID: https://orcid.org/0000-0003-1539-2142)
- Michael P. East (ORCID: https://orcid.org/0000-0002-1994-6117)
- Carrow I. Wells (ORCID: https://orcid.org/0000-0003-4799-6792)
- Timothy M. Willson (ORCID: https://orcid.org/0000-0003-4181-8223)
- Lee M. Graves (ORCID: https://orcid.org/0000-0002-4736-9855)
- James M. Bennett (ORCID: https://orcid.org/0000-0003-1396-8400)
- Graham J. Tizzard (ORCID: https://orcid.org/0000-0003-1901-0607)
Institutions
- University of North Carolina at Chapel Hill (US)
Publication Details
- Journal
- UNC Libraries
- Published
- 2025-10-11
- DOI
- https://doi.org/10.17615/6ptm-8s66
- Primary Topic
- Cancer-related Molecular Pathways
- Type
- article
- Field-Weighted Citation Impact
- 0.00