Carolyn D Dzierba, Bireshwar Dasgupta, George Karageorge, Walter Kostich, Brian Hamman, Jason Allen, Kim M Esposito, Ramesh Padmanabha, James Grace, Kimberley Lentz, John Morrison, Daniel Morgan, Amy Easton, Clotilde Bourin, Marc R Browning, Ramkumar Rajamani, Andrew Good, Dawn D Parker, Jodi K Muckelbauer, Javed Khan, Daniel Camac, Kaushik Ghosh, Vivek Halan, Jonathan S Lippy, Kenneth S Santone, R Rex Denton, Ryan Westphal, Linda J Bristow, Charles M Conway, Joanne J Bronson, John E Macor
Adaptor protein 2-associated kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases and plays a role in modulating receptor endocytosis. AAK1 was identified as a potential therapeutic target for the treatment of neuropathic pain when it was shown that AAK1 knock out (KO) mice had a normal response to the acute pain phase of the mouse formalin model, but a reduced response to the persistent pain phase. Herein we report our early work investigating a series of pyrrolo[2,1- f ][1,2,4]triazines as part of our efforts to recapitulate this KO phenotype with a potent, small molecule inhibitor of AAK1...
June 3, 2023: Medicinal Chemistry Research