Optimized Chemical Probes for REV-ERB伪

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• 作者：Ryan P. Trump ; 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
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：June 13, 2013
• 年：2013
• 卷：56
• 期：11
• 页码：4729-4737
• 全文大小：327K
• 年卷期：v.56,no.11(June 13, 2013)
• ISSN：1520-4804

文摘

REV-ERB伪 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-ERB伪 agonists based on GSK4112 (1) for potency, selectivity, and bioavailability.f(event, 'ref1'); return false;" href="JavaScript:void(0);" class="ref">(1) Potent REV-ERB伪 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 LXR伪. Amine 4 demonstrated in vivo bioavailability after either iv or oral dosing.