| Literature DB >> 32435390 |
Simona De Marino1, Claudia Finamore1, Michele Biagioli2, Adriana Carino2, Silvia Marchianò2, Rosalinda Roselli1, Cristina Di Giorgio2, Martina Bordoni2, Francesco Saverio Di Leva1, Ettore Novellino1, Chiara Cassiano1, Vittorio Limongelli1,3, Angela Zampella1, Carmen Festa1, Stefano Fiorucci2.
Abstract
GPBAR1 agonists have been identified as potential leads for the treatment of diseases related to colon inflammation such as Crohn's and ulcerative colitis. In this paper, we report the discovery of a small library of hyodeoxycholane analogues, decorated at C-6 with different substituents, as potent and selective GPBAR1 agonists. In vitro pharmacological assays showed that compound 6 selectively activates GPBAR1 (EC50 = 0.3 μM) and reduces the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in THP1 cells. The binding mode of compound 6 in GPBAR1 was elucidated by docking calculations. Moreover, compound 6 protects against TNBS-induced colitis in Gpbar1+/+ rodent model, representing an intriguing lead for the treatment of these inflammatory disorders.Entities:
Year: 2020 PMID： 32435390 PMCID： PMC7236273 DOI： 10.1021/acsmedchemlett.9b00636
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345