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 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.