Background:

IC50: 670 nM for REV-ERB-α and 800 nM for REV-ERB-β

SR9009, also known as Stenabolic, is a research drug as agonist of REV-ERB.

REV-ERB-α and REV-ERB-β, two nuclear receptors, have a critical role in regulating the expression of core clock proteins driving rhythms in activity and metabolism.

In vitro: Both SR9009 and its analog SR9011 could dose-dependently increase the REV-ERB-dependent repressor activity assessed in HEK293 cells expressing a chimaeric Gal4 DNA binding domain: REV-ERB ligand binding domain α or β and a Gal4-responsive luciferase reporter. In addition, SR9009 was found to be able to suppress BMAL1 messenger RNA expression in HepG2 cells in a REV-ERB-α/β-dependent manner [1].

In vivo: Mice were treated with a single dose of SR9009, SR9011 or vehicle at circadian time 6 (CT6 (6h after lights on) after 12 days in D/D conditions showing peak expression of Rev-erb-α. Results showed that vehicle injection caused no disruption in circadian locomotor activity. In contrast, administration of a single dose of either SR9009 or SR9011 led to the loss of locomotor activity during the subject dark phase. In addition, the normal activity returned the next circadian cycle, which was consistent with clearance of the drugs in less than 24h [1].

Clinical trial: Up to now, SR9009 is still in the preclinical development stage.

Reference:
[1] Solt LA,Wang Y,Banerjee S,Hughes T,Kojetin DJ,Lundasen T,Shin Y,Liu J,Cameron MD,Noel R,Yoo SH,Takahashi JS,Butler AA,Kamenecka TM,Burris TP.  Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature.2012 Mar 29;485(7396):62-8.