Mirabegron (YM-178) vs SLU-PP-915

Metabolic

Metabolic

Research Only

Research Only

Mirabegron selectively activates the human β3-adrenergic receptor with reported low-nanomolar potency (~22.4 nM EC50 for cAMP accumulation in vitro, label-corroborated) and approximately 500-fold lower activity at β1/β2 receptors. Clinically, β3-AR activation relaxes detrusor smooth muscle during bladder storage, increasing capacity without impairing voiding contractions. β3-AR is also expressed on human brown and beige adipose tissue, where agonism increases thermogenesis and metabolic rate—the basis for investigational metabolic studies.

The estrogen-related receptors (ERRα/β/γ) are orphan nuclear receptors that act as master transcriptional regulators of oxidative metabolism, driving mitochondrial biogenesis, oxidative phosphorylation, fatty-acid oxidation, and the TCA cycle — largely as partners of the PGC-1 coactivators. SLU-PP-915 binds and activates all three ERR isoforms with an EC50 of roughly 400 nM at each. In its medicinal-chemistry design, the phenol and aniline groups of earlier ERR agonists were replaced with a boronic-acid moiety on a disubstituted thiophene scaffold, which preserved receptor activity while improving microsomal metabolic stability and oral exposure. In cells and in rodents it upregulates canonical ERR target genes including PGC-1α, lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase 4 (PDK4), and DNA-damage-inducible transcript 4 (DDIT4).

Not established in humans; engineered for improved metabolic stability and oral exposure relative to first-generation ERR agonists