Identification and Optimization of 4-Anilinoquinolines as Inhibitors of Cyclin G Associated Kinase

Asquith, C. R. M.; Laitinen, T.; Bennett, J. M.; Godoi, P. H.; Tizzard, G. J.; Elkins, J. M.; Willson, T. M.; Zuercher, W. J.

doi:10.1101/117630

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bioRxiv · 10.1101/117630

Identification and Optimization of 4-Anilinoquinolines as Inhibitors of Cyclin G Associated Kinase

Asquith, C. R. M.·Laitinen, T.·Bennett, J. M.·Godoi, P. H.·Tizzard, G. J.·Elkins, J. M.·Willson, T. M.·Zuercher, W. J.

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Abstract

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 and over 50,000-fold selectivity relative to other members of the numb-associated kinase (NAK) sub-family. These compounds may be useful tools to explore the therapeutic potential of GAK in prevention of a broad range of infectious diseases.

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Asquith, C. R. M., Laitinen, T., Bennett, J. M., Godoi, P. H., Tizzard, G. J., Elkins, J. M., Willson, T. M., Zuercher, W. J.. 2017-03-16. Identification and Optimization of 4-Anilinoquinolines as Inhibitors of Cyclin G Associated Kinase. https://doi.org/10.1101/117630

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