Skip to content
AnimalExercise mimetic targeting mitochondrial energy pathways

SLU-PP-322

Also indexed as SLU PP 322, ERR agonist SLU-PP-322

SLU-PP-322 is a synthetic small-molecule agonist of estrogen-related receptors (ERRα, ERRβ, and ERRγ) developed at Saint Louis University. It mimics the metabolic effects of sustained aerobic exercise at the cellular level, promoting mitochondrial biogenesis, fatty acid oxidation, and endurance capacity without physical activity. In preclinical animal studies, it has demonstrated significant improvements in exercise performance, fat metabolism, and cardiac function.

Overview

SLU-PP-322 distributes to tissues with high ERR expression — particularly cardiac and skeletal muscle — where it modulates nuclear receptor transcriptional activity. The downstream effects include upregulation of mitochondrial biogenesis markers (TFAM, NRF1, NRF2), increased expression of fatty acid oxidation enzymes (HADHA, ACADL), and enhanced OXPHOS complex expression. Pharmacokinetically, as a small molecule it likely undergoes hepatic first-pass metabolism (CYP450 pathways) with renal/fecal excretion; however, formal PK/PD data in mammals beyond rodents is not publicly available.

Proposed mechanism

SLU-PP-322 acts as a pan-agonist of the estrogen-related receptor (ERR) family — specifically ERRα, ERRβ, and ERRγ — which are orphan nuclear receptors that regulate transcriptional programs governing mitochondrial biogenesis and oxidative metabolism. Upon binding these receptors, it activates downstream gene networks including PGC-1α co-activation, upregulation of fatty acid oxidation enzymes, and increased mitochondrial density in skeletal muscle and cardiac tissue. This pharmacologically replicates many of the transcriptional adaptations observed after sustained aerobic exercise training.

What the evidence supports

Most data comes from preclinical animal studies. Human clinical trial evidence is limited or absent.

Graded Animal

Evidence drawn from in vivo animal models or in vitro systems. Mechanistically informative; translation to humans is unproven.

Key citations

Representative primary sources, including results that did not favour the compound.

  1. [1]

    Targeting Estrogen-Related Receptors with a Pan-Agonist Disrupts Cancer Cell Metabolism and Proliferation

    · Nature Chemical Biology (SLU research group publications on ERR agonism) · 2022

  2. [2]

    Estrogen-related receptors in metabolism and disease: an update

    · Trends in Endocrinology and Metabolism, doi:10.1016/j.tem.2019.03.006 · 2019

  3. [3]

    ERRγ is required for the metabolic maturation of therapeutically functional glucose-stimulated insulin secretion

    · Cell Metabolism, doi:10.1016/j.cmet.2014.05.012 · 2014

Citation records in this build are illustrative placeholders for the design.

Reference information for research purposes. Not medical advice, and not a recommendation to use any compound. Many entries describe substances that are not approved for human use.

Related profiles

ACTH 1-39

Clinical

Full-length adrenal hormone with broad receptor activity

ACTH 1-39 is the full-length, biologically active form of adrenocorticotropic hormone, a 39-amino acid peptide naturally secreted by the anterior pituitary gland. It primarily stimulates the adrenal cortex to produce cortisol, aldosterone, and adrenal androgens. Beyond adrenal signaling, ACTH 1-39 exerts direct effects on the brain, immune system, and peripheral tissues via melanocortin receptors.

0 RCT · 0 human · 0 preclinical

Immune

Adipotide (FTTP)

Animal

Targeted fat-depot destruction via vascular apoptosis

Adipotide (also called FTTP) is an experimental peptidomimetic compound designed to selectively destroy the blood supply to white adipose tissue by targeting prohibitin, a protein highly expressed on the vasculature feeding fat cells. Originally developed at MD Anderson Cancer Center, it demonstrated dramatic fat loss in obese rhesus monkeys without dietary restriction. It remains a research compound with no approved human clinical use.

0 RCT · 0 human · 0 preclinical

fat-loss

AICAR

Human-limited

AMPK activator mimicking endurance exercise effects

AICAR (Acadesine) is a nucleoside analog and potent AMPK activator that mimics the cellular energy-depletion state, triggering a cascade of metabolic adaptations including enhanced fatty acid oxidation and mitochondrial biogenesis. It has been extensively studied for its ability to improve endurance performance, insulin sensitivity, and metabolic flexibility without physical exercise. Originally developed as a cardioprotective agent, it has attracted significant interest in the performance and longevity research communities.

0 RCT · 0 human · 0 preclinical

metabolic