Optimized chemical probes for REV-ERB alpha

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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

LanguageEnglish
Pages4729-4737
Number of pages9
JournalJournal of Medicinal Chemistry
Volume56
Issue number11
DOIs
Publication statusPublished - 13 Jun 2013

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Biological Availability
Physiology
Circadian Rhythm
Amines
Interleukin-6
Cells

Keywords

  • rhythms
  • ligand
  • GSK4112
  • beta
  • cells
  • modulation
  • circadian behaviour
  • metabolism
  • macrophages
  • clock

Cite this

Trump, R. P., Bresciani, S., Cooper, A. W. J., Tellam, J. P., Wojno, J., Blaikley, J., ... Tomkinson, N. C. O. (2013). Optimized chemical probes for REV-ERB alpha. Journal of Medicinal Chemistry, 56(11), 4729-4737. https://doi.org/10.1021/jm400458q
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. / Optimized chemical probes for REV-ERB alpha. In: Journal of Medicinal Chemistry. 2013 ; Vol. 56, No. 11. pp. 4729-4737.
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Trump, RP, Bresciani, S, Cooper, AWJ, Tellam, JP, Wojno, J, Blaikley, J, Orband-Miller, LA, Kashatus, JA, Boudjelal, M, Dawson, HC, Loudon, A, Ray, D, Grant, D, Farrow, SN, Willson, TM & Tomkinson, NCO 2013, 'Optimized chemical probes for REV-ERB alpha' Journal of Medicinal Chemistry, vol. 56, no. 11, pp. 4729-4737. https://doi.org/10.1021/jm400458q

Optimized chemical probes for REV-ERB alpha. / 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.

In: Journal of Medicinal Chemistry, Vol. 56, No. 11, 13.06.2013, p. 4729-4737.

Research output: Contribution to journalArticle

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AU - Cooper, Anthony W. J.

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AU - Ray, David

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AU - Willson, Timothy M.

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Trump RP, Bresciani S, Cooper AWJ, Tellam JP, Wojno J, Blaikley J et al. Optimized chemical probes for REV-ERB alpha. Journal of Medicinal Chemistry. 2013 Jun 13;56(11):4729-4737. https://doi.org/10.1021/jm400458q