SLU-PP-332 AND RELATED ERRα AGONISTS: A FOCUSED MINIREVIEW OF METABOLIC REGULATION, AND THERAPEUTIC POTENTIAL

Mostafa Essam Eissa

doi:10.22270/ujpr.v10i3.1355

Mostafa Essam Eissa Independent Researcher and Consultant, Cairo, Egypt.

10.22270/ujpr.v10i3.1355

Keywords:

ERRα agonist, exercise mimetic, metabolic syndrome, mitochondrial biogenesis, obesity, type 2 diabetes

Abstract

The global burden of metabolic disorders, including obesity and type 2 diabetes, necessitates innovative therapeutic strategies. SLU-PP-332, a synthetic agonist of estrogen-related receptor α (ERRα), has emerged as a promising exercise mimetic, demonstrating preclinical efficacy in enhancing mitochondrial biogenesis, insulin sensitivity, and energy expenditure. This brief review synthesizes current knowledge on SLU-PP-332 and related ERRα agonists, highlighting their molecular mechanisms, preclinical outcomes, translational challenges, and ethical considerations. ERRα activation by SLU-PP-332 upregulates peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), driving fatty acid oxidation and mimicking exercise-induced metabolic adaptations. However, pan-ERR activity raises concerns about off-target effects such as cardiac hypertrophy and hepatotoxicity. Despite robust preclinical data, clinical translation remains hindered by the absence of human trials and undefined long-term safety. Future research must prioritize isoform-selective agonist design, rigorous clinical validation, and equitable access frameworks.