1 research outputs found
Optimized Chemical Probes for REV-ERBα
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 (<b>1</b>) for potency, selectivity,
and bioavailability. Potent REV-ERBα
agonists <b>4</b>, <b>10</b>, <b>16</b>, and <b>23</b> are detailed for their ability to suppress BMAL and IL-6
expression from human cells while also demonstrating excellent selectivity
over LXRα. Amine <b>4</b> demonstrated in vivo bioavailability
after either iv or oral dosing