SLU-PP-332

What Is SLU-PP-332?

SLU-PP-332 is a small-molecule synthetic pan-agonist of the three estrogen-related receptors ERRalpha, ERRbeta, and ERRgamma, not a peptide. These are orphan nuclear receptors expressed heavily in mitochondria-rich tissues (skeletal muscle, heart, brown fat, liver), where they sit upstream of PGC-1alpha, the master regulator of mitochondrial biogenesis. When SLU-PP-332 stabilises ERRalpha in its active conformation, the receptor transcribes the same gene programme that endurance exercise induces: PGC-1alpha upregulation, increased mitochondrial density, induction of fatty-acid oxidation enzymes (CPT1B, ACADM, HADHA), and expression of electron transport chain subunits.

The cell therefore behaves as though it has been trained, even at rest, which is why the compound is described as an exercise mimetic: it does not replicate the cardiovascular work of training, but it reproduces the downstream metabolic adaptation. It was developed in the Burris and Patti laboratories at Saint Louis University, hence the SLU prefix. In the 2023 mouse studies, treated animals ran about 70% longer and 45% further than controls and showed reduced fat gain on a high-fat diet. All published efficacy is preclinical; no human pharmacokinetic, efficacy, or safety data exist, and no clinical trial has been registered.