| Literature DB >> 23656296 |
Ryan P Trump1, Stefano Bresciani, Anthony W J Cooper, James P Tellam, Justyna Wojno, John Blaikley, Lisa A Orband-Miller, Jennifer A Kashatus, Mohamed Boudjelal, Helen C Dawson, Andrew Loudon, David Ray, Daniel Grant, Stuart N Farrow, Timothy M Willson, Nicholas C O Tomkinson.
Abstract
REV-ERBα has emerged as an important target for regulation of circadian rhythm and its associated physiology. Herein, we report on the optimization of a series of REV-ERBα agonists based on GSK4112 (1) for potency, selectivity, and bioavailability. (1) Potent REV-ERBα agonists 4, 10, 16, and 23 are detailed for their ability to suppress BMAL and IL-6 expression from human cells while also demonstrating excellent selectivity over LXRα. Amine 4 demonstrated in vivo bioavailability after either iv or oral dosing.Entities:
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Year: 2013 PMID： 23656296 PMCID： PMC4347663 DOI： 10.1021/jm400458q
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446