Autoimmune pathways in mice and humans are blocked by pharmacological stabilization of the TYK2 pseudokinase domain

Authors: James R. Burke, Lihong Cheng, Kathleen M. Gillooly, Joann Strnad, Adriana Zupa-Fernandez, Ian M. Catlett, Yifan Zhang, Elizabeth Heimrich, Kim W. McIntyre, Mark Cunningham, Julie Carman, Xiadi Zhou, Dana Banas, Charu Chaudhry, Sha Li, Celia D’Arienzo, Anjaneya Chimalakonda, Xiaoxia Yang, Jenny Xie, Jian Pang, Qihong Zhao, Shawn Rose, Jinwen Huang, Ryan Moslin, Stephen T. Wrobleski, David S. Weinstein, Luisa Salter–Cid - Science Translational Medicine 2019 cited by 282

1, B cells, and myeloid cells integral to autoimmunity were blocked by BMS-986165, both in vitro and in vivo in a phase 1 clinical trial. BMS-986165 demonstrated robust efficacy, consistent with blockade of multiple autoimmune pathways, in murine models of lupus nephritis and inflammatory bowel disease, supporting its therapeutic potential for multiple immune-mediated diseases.