Optimized chemical probes for REV-ERBα
RP Trump, S Bresciani, AWJ Cooper… - Journal of medicinal …, 2013 - ACS Publications
RP Trump, S Bresciani, AWJ Cooper, JP Tellam, J Wojno, J Blaikley, LA Orband-Miller…
Journal of medicinal chemistry, 2013•ACS PublicationsREV-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. 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.
associated physiology. Herein, we report on the optimization of a series of REV-ERBα
agonists based on GSK4112 (1) for potency, selectivity, and bioavailability. 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.
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. 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.
ACS Publications