| Literature DB >> 32334911 |
Lalgudi S Harikrishnan1, Patrice Gill2, Muthoni G Kamau2, Lan-Ying Qin2, Zheming Ruan2, Daniel O'Malley2, Tram Huynh2, Sylwia Stachura2, Cullen L Cavallaro2, Zhonghui Lu2, James J-W Duan2, Carolyn A Weigelt3, John S Sack3, Max Ruzanov3, Javed Khan3, Murali Gururajan4, Jessica J Wong4, Yanling Huang4, Melissa Yarde5, Zhuyin Li5, Cliff Chen6, Huadong Sun6, Virna Borowski7, Anwar Murtaza7, Brian E Fink2.
Abstract
Substituted benzyloxy aryl compound 2 was identified as an RORγt agonist. Structure based drug design efforts resulted in a potent and selective tricyclic compound 19 which, when administered orally in an MC38 mouse tumor model, demonstrated a desired pharmacokinetic profile as well as a dose-dependent pharmacodynamic response. However, no perceptible efficacy was observed in this tumor model at the doses investigated.Entities:
Keywords: ROR gamma; RORgt; RORγt; Retinoic acid related orphan receptor; TH17 cells and IL-17
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Year: 2020 PMID： 32334911 DOI： 10.1016/j.bmcl.2020.127204
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823