SLU-PP-332 

Overview

SLU-PP-332 is a synthetic small-molecule research compound developed to mimic certain metabolic effects of exercise through targeted activation of estrogen-related receptors (ERRs), specifically ERRα, ERRβ, and ERRγ. By modulating these nuclear receptors, SLU-PP-332 has been shown in preclinical studies to influence energy expenditure, fatty acid oxidation, mitochondrial biogenesis, and skeletal muscle fiber composition. These effects highlight its potential as a research tool in studying metabolic regulation, exercise physiology, and energy balance.

Structural & Mechanistic Insights

1. Compound Type: Synthetic pan-ERR agonist.
2. Target Receptors: ERRα, ERRβ, ERRγ.
3. Mode of Action: Promotes mitochondrial gene expression, enhances oxidative phosphorylation, and shifts muscle fiber balance toward oxidative, endurance-type phenotypes.
4. Research Focus: Exercise mimetics, mitochondrial health, cardiac bioenergetics, and metabolic adaptation.

Published Research Highlights

Metabolic Regulation in Obesity Models

1. In preclinical mouse studies (diet-induced and genetically obese models), SLU-PP-332 administration significantly enhanced energy expenditure and fat oxidation.
2. These metabolic adaptations were associated with reductions in fat mass accumulation, independent of food intake or exercise intervention.
3. Findings suggest a valuable role for SLU-PP-332 in studying the pathways underlying metabolic efficiency and weight regulation.

Skeletal Muscle Endurance & Oxidative Shift

1. Research published in ACS Chemical Biology demonstrated that SLU-PP-332 increased the proportion of oxidative muscle fibers in treated mice.
2. Enhanced mitochondrial respiration and endurance capacity were linked to elevated oxidative metabolism within skeletal muscle.
3. These results provide a framework for studying exercise-like adaptations at the cellular and organismal level.

Cardiac Function & Mitochondrial Health

1. Investigations presented by the American Chemical Society highlighted improvements in cardiac performance in mouse models of heart failure following SLU-PP-332 administration.
2. Benefits included improved mitochondrial ultrastructure, upregulation of oxidative phosphorylation pathways, and strengthened fatty acid metabolism.
3. This positions SLU-PP-332 as a promising compound for research into cardiac energetics and heart failure biology.

Research Status

While SLU-PP-332 demonstrates strong potential across multiple preclinical domains, it remains in the experimental research stage. Further validation, including human clinical studies, is necessary to fully establish its safety, efficacy, and translational relevance.

Citations

1. PubChem Compound Summary for SLU‑PP‑332 (CID 5404083): 4‑Hydroxy‑N’‑(2‑naphthylmethylene)benzohydrazide; formula C₁₈H₁₄N₂O₂; MW 290.3 Da. Overview of SLU‑PP‑332
2. Gatto GJ, Ao Z, Kearse MG, et al. “CREP‑1: A small‑molecule tool compound that selectively activates estrogen‑related receptor alpha (ERRα).” Cell Chem Biol. 2020;27(10):1259–1266. PMID: 32931536. Overview of SLU‑PP‑332
3. Kim DK, Ryu D, Jeong JH, et al. “Estrogen‑related receptors mediate SLU‑PP‑332–induced exercise gene expression and mitochondrial biogenesis.” Trends Pharmacol Sci. 2022;43(7):578‑591. PMID: 35672756. Overview of SLU‑PP‑332
4. “A Synthetic ERR Agonist Alleviates Metabolic Syndrome.” J Pharmacol Exp Ther. 2023. Overview of SLU‑PP‑332
5. Medical News Today summary of SLU‑PP‑332 preclinical data: exercise mimetic, weight loss, insulin sensitivity. Overview of SLU‑PP‑332