Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro and animal experimental study with no human data.
PubMed 36988910 · doi:10.1021/acschembio.2c00720
What was done
Researchers identified and evaluated SLU-PP-332, a synthetic pan-agonist of estrogen receptor-related receptors (ERRα, ERRβ, and ERRγ) with highest potency against ERRα. They evaluated its pharmacokinetic profile in vivo, measured its effects on cellular respiration and mitochondrial function in a skeletal muscle cell line, and tested its impact on muscle fiber composition, exercise-related gene expression, and endurance performance in mice.
What was found
The abstract reports no quantitative data or effect sizes. Qualitatively, SLU-PP-332 enhanced mitochondrial function and cellular respiration in cultured skeletal muscle cells. In mice, administration of the compound induced an ERRα-dependent acute aerobic exercise genetic program, increased type IIa oxidative muscle fibers, and enhanced exercise endurance.
Why it matters
This study provides proof-of-concept for developing synthetic ERRα agonists as exercise mimetics to stimulate oxidative muscle adaptations and improve physical performance in metabolic disease and aging.
Limits
Findings are limited to cell culture and mouse models. The abstract does not disclose sample sizes, treatment duration, dosage, pharmacokinetic metrics, or magnitude of endurance gains. Human efficacy, tolerability, and off-target risks are unstudied.
Cited by
- supports SLU-PP-332 functions as an exercise mimetic by acting as an agonist at the estrogen receptor-related receptor alpha.