SLU-PP-332

Overview

SLU-PP-332 is a small-molecule agonist of estrogen-related receptor alpha (ERRalpha) studied as an exercise mimetic for its ability to activate transcriptional programs associated with aerobic exercise adaptation, including mitochondrial biogenesis and muscle fiber-type switching.

Mechanism of Action

SLU-PP-332 activates ERRalpha, an orphan nuclear receptor that regulates oxidative metabolism gene programs. Activation upregulates PGC-1alpha co-activator pathways, driving mitochondrial biogenesis (TFAM, NRF1), fatty acid oxidation (CPT1B, ACADM), and slow-twitch type I muscle fiber specification. Note: despite the name, ERRalpha does not bind estrogen.

Research Summary

Billon et al. demonstrated that SLU-PP-332 in sedentary mice increased treadmill endurance ~50%, increased slow-twitch fibers, enhanced mitochondrial content, and conferred resistance to high-fat diet weight gain without exercise training. Developed at Saint Louis University. No human clinical trials initiated.

Dosing Information

Reported Side Effects

• Limited human safety data
• Transient reduction in white blood cell counts (murine)
• Mild gastrointestinal effects (preclinical)
• Potential estrogen signaling interaction (preclinical)

Research References

• Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity (2023)
• A Synthetic ERR Agonist Alleviates Metabolic Syndrome (2023)