Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1021/jm400458q

Type

Journal article

Journal

J Med Chem

Publication Date

13/06/2013

Volume

56

Pages

4729 - 4737

Keywords

Amines, Animals, Biological Availability, Carrier Proteins, Cell Line, Circadian Rhythm, Glycine, Humans, Liver X Receptors, Mice, Mice, Inbred C57BL, Nuclear Receptor Subfamily 1, Group D, Member 1, Orphan Nuclear Receptors, Peptide Fragments, Radioligand Assay, Structure-Activity Relationship, Thiophenes