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- PMID: 23656296
- UKPMCID: 23656296
- DOI: 10.1021/jm400458q
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Optimized chemical probes for REV-ERBα.
Trump, Ryan P; Bresciani, Stefano; Cooper, Anthony W J; Tellam, James P; Wojno, Justyna; Blaikley, John; Orband-Miller, Lisa A; Kashatus, Jennifer A; Boudjelal, Mohamed; Dawson, Helen C; Loudon, Andrew; Ray, David; Grant, Daniel; Farrow, Stuart N; Willson, Timothy M; Tomkinson, Nicholas C O
Journal of medicinal chemistry. 2013;56(11):4729-37.
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Full-text held externally
- PMID: 23656296
- UKPMCID: 23656296
- DOI: 10.1021/jm400458q
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.