Buy SLU-PP-332 Powder

Description

CAS number: 303760-60-3

What is SLU-PP-332?

SLU-PP-332 is a synthetic small molecule developed at Saint Louis University as a pharmacological tool for studying estrogen-related receptor (ERR) biology. It is not a peptide. It belongs to the medications collection because it is a small-molecule compound, not a peptide-based therapeutic. Searches for “slu pp 332 peptide” reflect a common misclassification; structurally and pharmacologically, it is a synthetic ligand for nuclear transcription factors.

The compound was first characterized by Billon, Sitaula, Banerjee, and colleagues from the Burris laboratory at Saint Louis University, published in ACS Chemical Biology in 2023, as a pan-agonist of ERRα, ERRβ, and ERRγ — the three members of the estrogen-related receptor subfamily. Unlike estrogen receptors (ERα, ERβ), estrogen-related receptors do not bind estrogen. They are constitutively active transcription factors that regulate mitochondrial biogenesis, oxidative phosphorylation, and fatty acid metabolism. SLU-PP-332 was designed as a research tool to activate all three ERR subtypes simultaneously and study what that activation produces in living systems.

How SLU-PP-332 works: The ERR pathway

Estrogen-related receptors and mitochondrial metabolism

Estrogen-related receptors are nuclear transcription factors that were identified in 1988 by Giguère and colleagues based on sequence homology to estrogen receptors. Despite their name, they are regulated by cellular energy status rather than by estrogen itself. As a 2015 review by Huss, Garbacz, and Xie in Biochimica et Biophysica Acta established, ERRs are constitutively active transcription factors that regulate genes central to oxidative phosphorylation, fatty acid oxidation, and mitochondrial biogenesis. A 2024 comprehensive review by Spinelli, Bruschi, Passalacqua, and colleagues in the International Journal of Molecular Sciences further characterized ERRα as a master regulator of glucose and lipid homeostasis across multiple tissues, identifying it as a target of interest for metabolic disease. The rationale for pharmacologically activating ERRs follows from this biology: if these receptors orchestrate the metabolic machinery that aerobic exercise upregulates, an agonist might recapitulate elements of that machinery without the exercise itself.

ERRα, ERRβ, and ERRγ: What each subtype contributes

ERRα is the most extensively studied of the three subtypes and has the strongest established link to skeletal muscle function. A 2023 study by Wattez, Eury, Hazen, and colleagues in Molecular Metabolism demonstrated that skeletal-muscle-specific combined ERRα/γ double knockout produced pale, oxidatively impaired muscles and severe exercise intolerance in mice — with dmKO animals unable to switch to lipid utilization during running — establishing that ERR activity is necessary for normal aerobic capacity. Independent work from the Evans laboratory confirmed the gain-of-function counterpart: a 2023 study by Xia, Scholtes, Dufour, and colleagues in Molecular Metabolism showed that genetic activation of ERRα in mouse skeletal muscle drove myofiber aerobic transformation — increased oxidative myofibers, angiogenesis, mitochondrial biogenesis, and fat oxidation — and enhanced running endurance and fatigue-resistance without exercise training. ERRγ contributes complementary roles in cardiac and oxidative fiber programming. A 2023 review by Sopariwala, Nguyen, and Narkar in the International Journal of Sports Medicine summarized estrogen-related receptor signaling across skeletal muscle fitness, noting that the ERR family collectively drives the transcriptional shift toward oxidative metabolism that characterizes trained muscle. A 2025 study by Fan, Oh, Wang, and colleagues published in PNAS provided direct mechanistic support, showing that ERRα, ERRβ, and ERRγ together regulate innate and adaptive mitochondrial energetics in mouse muscle in a manner that tracks with exercise-induced adaptation.

Why pan-agonism matters for the exercise mimetic hypothesis

SLU-PP-332 is designed as a pan-agonist — it activates all three ERR subtypes rather than targeting a single one. Earlier ERR tool compounds were subtype-selective; the medicinal chemistry program that produced SLU-PP-332 was aimed at generating a compound capable of activating the full ERR program simultaneously. A 2020 medicinal chemistry study by Shahien, Elagawany, Sitaula, and colleagues in Bioorganic Chemistry described the conversion of GSK4716 (an ERRβ/γ-selective agonist) to pan-ERR agonists, establishing the chemical rationale for the SLU-PP chemotype. The Burris laboratory’s broader medicinal chemistry work, including a 2020 paper by Schoepke, Billon, Haynes, and colleagues in ACS Chemical Biology characterizing SLU-PP-1072 (a selective ERRα/γ inverse agonist from the same platform), demonstrates that this is an active tool-compound chemistry program — not a clinical development program. SLU-PP-332 was built to answer mechanistic questions in research settings, not to enter clinical development.

The connection to PGC-1α and established exercise biology

ERRs do not operate in isolation. They work in concert with PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), the transcriptional coactivator considered the master regulator of mitochondrial biogenesis. A 2020 review by Islam, Hood, and Gurd in Applied Physiology, Nutrition, and Metabolism catalogued the regulators of exercise-induced skeletal muscle mitochondrial biogenesis beyond PGC-1α and identified ERRα as one of the key downstream effectors. ERRα is simultaneously a target of PGC-1α and an upstream regulator of PGC-1α’s own transcriptional targets, forming a regulatory loop that amplifies the mitochondrial response to exercise.