ERR-alpha Program

Recently it has been discovered that ERRα (NR3B1) plays a critical role in controlling energy expenditure. ERRα k.o. mice show an "athletic" lean phenotype which can be at least partially explained by ERRα interacting with PGC-1, a cofactor known for regulating energy metabolism in fat and muscle tissues. Moreover, a direct involvement of ERRα, together with PGC-1 could be demonstrated for the induction of so-called OXPHOS genes, i.e. for genes that lead to mitochondrial biogenesis and induction of oxidative phosphorylation metabolism. Stimulation of the ERRα / PGC-1 couple in skeletal muscle leads to a switch from glucose consuming fast twitch ("white") muscle fibers towards oxidative metabolism-based slow twitch ("red") fibers. Thus it appears as if ERRα shifts the balance from glucose consumption towards fatty acid burning in cardiac and skeletal muscle. With this effect, ERRα shows a good profile as a target for an anti-obesity / metabolic syndrome drug.

Phenex has identified hit series out of its proprietary screening collection, that selectively modulate the activity of ERRα.