Cardarine (GW-501516) vs SLU-PP-915

Metabolic

Metabolic

Research Only

Research Only

GW-501516 is a potent, subtype-selective agonist of PPARδ (PPARβ/δ). In skeletal muscle it activates PGC-1-dependent programs for fatty-acid uptake, β-oxidation, and mitochondrial energy uncoupling, promoting fat oxidation; in macrophages it induces ABCA1 and reverse cholesterol transport. In mice, combined with exercise training it reprogrammed muscle-fiber metabolism to increase endurance (Narkar et al., Cell 2008). It does not act on the androgen receptor and is not a SARM.

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