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Abstract
REV-ERB alpha 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 alpha agonists based on G5K4112 (1) for potency, selectivity, and bioavailability.(1) Potent REV-ERB alpha 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 LAR alpha. Amine 4 demonstrated in vivo bioavailability after either iv or oral dosing.
Original language | English |
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Pages (from-to) | 4729-4737 |
Number of pages | 9 |
Journal | Journal of Medicinal Chemistry |
Volume | 56 |
Issue number | 11 |
DOIs | |
Publication status | Published - 13 Jun 2013 |
Keywords
- rhythms
- ligand
- GSK4112
- beta
- cells
- modulation
- circadian behaviour
- metabolism
- macrophages
- clock
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Dive into the research topics of 'Optimized chemical probes for REV-ERB alpha'. Together they form a unique fingerprint.Projects
- 1 Finished
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SMSdrug.net: Alignment Of Synthesis, Medicinal Chemistry And Strucrural Genomics To Accelerate Uk Drug Discovery: Network SMS-Drug
Tomkinson, N. (Principal Investigator), C. Bagley, M. (Academic), Feilden, H. (Academic), Johnston, B. (Academic), Knapp, S. (Academic), MacKay, S. (Academic), Overington, J. (Academic) & Spencer, J. (Academic)
EPSRC (Engineering and Physical Sciences Research Council)
1/09/11 → 31/08/15
Project: Research