Ashley L Ramos, Eric R Goedken, Kristine E Frank, Maria A Argiriadi, Sana Bazzaz, Zhiguo Bian, Jesse T C Brown, Paolo A Centrella, Hui-Ju Chen, Jeremy S Disch, Pamela L Donner, David B Duignan, Diana Gikunju, Stephen N Greszler, Marie-Aude Guié, Sevan Habeshian, Hajnalka E Hartl, Christopher D Hein, Charles W Hutchins, Rachael Jetson, Anthony D Keefe, Hasan Khan, Huan-Qiu Li, Allison Olszewski, Benjamin J Ortiz Cardona, Augustine Osuma, Sanjay C Panchal, Ryan Phelan, Wei Qiu, J Brad Shotwell, Anurupa Shrestha, Myron Srikumaran, Zhi Su, Chaohong Sun, Anup K Upadhyay, Michael D Wood, Haihong Wu, Ruijie Zhang, Ying Zhang, Gang Zhao, Haizhong Zhu, Matthew P Webster
Dysregulation of IL17A drives numerous inflammatory and autoimmune disorders with inhibition of IL17A using antibodies proven as an effective treatment. Oral anti-IL17 therapies are an attractive alternative option, and several preclinical small molecule IL17 inhibitors have previously been described. Herein, we report the discovery of a novel class of small molecule IL17A inhibitors, identified via a DNA-encoded chemical library screen, and their subsequent optimization to provide in vivo efficacious inhibitors...
April 4, 2024: Journal of Medicinal Chemistry