Mechanism

How it works

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.

Reported in research

Benefits

Promotes mitochondrial biogenesis in skeletal and cardiac muscle (animal data)
Enhances fatty acid oxidation and reduces adiposity in preclinical models
Improves exercise endurance capacity without physical training in mice
May support cardiac metabolic efficiency and heart function in animal models

Context, not a prescription

Dosing

Typical range: Research dosing not established in humans; animal studies used ~50 mg/kg/day (not translatable to human dosing) (Subcutaneous, Oral)
Cycle length: Not established; animal studies ranged 4-8 weeks
Half-life: Not formally established; estimated short (~2-4 hours based on small-molecule kinetics)

Safety

Side effects & contraindications

Possible side effects

Unknown safety profile in humans — no clinical trials conducted
Potential off-target effects on estrogen-related signaling pathways
Possible cardiovascular effects due to ERR activity in cardiac tissue
Unknown hepatotoxicity risk at human-relevant doses

Contraindications

Human use not established — contraindications are speculative
Hormone-sensitive conditions (given ERR pathway modulation)
Pregnancy and breastfeeding (no safety data)
Pre-existing hepatic or cardiac conditions without medical supervision

Research information, not medical advice. Always consult a licensed clinician before considering any peptide.

In depth

Full profile

What it does

In animal models, researchers observed increased running endurance, reduced body fat, and improved heart function over 4-8 weeks. No human data is available to confirm these effects.

How it works

Imagine your cells are a factory. Normally, the factory upgrades its machinery and increases production only when it gets overwhelmed by demand — like during exercise. SLU-PP-322 is like a memo from management that says 'upgrade the machines and switch to the efficient fuel source' even when the factory is sitting idle.

The compound binds to specific proteins inside cells called estrogen-related receptors (ERRs). These proteins act like switches that, when activated, turn on the genes responsible for building mitochondria and burning fatty acids. The result is muscles that look and behave more like those of a trained athlete — at least in mice.

What to expect

Animal studies suggest metabolic changes begin within 1-2 weeks of consistent dosing, though no human onset data exists.

Week 1: In animal models, early upregulation of mitochondrial gene expression is observed. No human data available.
Weeks 2-4: Rodent studies show increased mitochondrial density in skeletal muscle and early improvements in endurance metrics.
Weeks 4-8: Animal studies demonstrate measurable reductions in fat mass, improved cardiac metabolic efficiency, and sustained endurance gains.

Good to know

Do not use outside of a controlled research environment
Consult a physician before considering any research compound
Understand that all available data is from rodent studies only

Staying safe

Unknown — no human safety data available
Possible hormonal disruption due to effects on estrogen-related receptor pathways

Avoid if you have:

Anyone with hormone-sensitive medical conditions
Pregnant or breastfeeding individuals
People with liver or heart conditions
Anyone not engaged in supervised research

Overview

Preclinical data demonstrates: increased mitochondrial volume density in Type I and IIa muscle fibers, elevated VO2max equivalent metrics in forced treadmill testing, reduced epididymal white adipose tissue mass, improved cardiac ejection fraction metrics, and a shift in respiratory exchange ratio (RER) toward preferential fat oxidation. ERRγ-specific activation in the heart may confer protective remodeling effects under metabolic stress.

How it works

ERRs function like master conductors of the mitochondrial orchestra. Under normal conditions, the baton (PGC-1α) is lifted only by exercise-induced signals like AMPK and CaMKII. SLU-PP-322 structurally mimics the ligand-binding domain stabilization that allows the receptor to recruit PGC-1α constitutively, effectively bypassing upstream kinase signaling to directly drive the transcriptional symphony of oxidative adaptation.

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.

Onset & timeline

In murine models, significant transcriptional upregulation of ERR target genes is detectable within 24-72 hours of initial dosing. Phenotypic changes in endurance capacity and fat oxidation rates emerge within 7-14 days of continuous administration at ~50 mg/kg/day in mice. Human onset is entirely speculative.

Days 1-3: Rapid nuclear receptor occupancy and coactivator recruitment; transcriptomic upregulation of ERR target genes detectable by RT-qPCR in animal models within 24h. Acute hemodynamic effects unknown.
Weeks 1-2: Measurable increases in mitochondrial marker proteins (TFAM, citrate synthase activity) in skeletal muscle biopsies from animal subjects. Early shifts in RER toward fat oxidation in metabolic cage studies.
Weeks 2-8: Sustained increases in exercise endurance (treadmill exhaustion testing), significant reduction in adipose mass, improved cardiac metabolic efficiency metrics, and stabilized ERR-driven transcriptional program in oxidative tissues.

Getting the most from it

Restrict use to in vitro or in vivo animal research contexts with appropriate IACUC oversight
Monitor hepatic enzyme panels (ALT, AST) in any animal study protocols
Avoid co-administration with PPARδ agonists (e.g., GW501516) until interaction profiles are characterized — additive metabolic stress possible

Common side effects

Potential ERR-mediated hormonal pathway disruption — ERRs share partial overlap with ERα signaling networks, raising theoretical concern for endocrine interference
Unknown hepatic metabolism burden — small molecule with likely CYP450 processing; hepatotoxicity risk uncharacterized

Mechanism of action

SLU-PP-322 functions as a pan-agonist for all three members of the estrogen-related receptor (ERR) subfamily: ERRα (NR3B1), ERRβ (NR3B2), and ERRγ (NR3B3). These orphan nuclear receptors regulate transcriptional programs governing mitochondrial biogenesis, oxidative phosphorylation, fatty acid β-oxidation, and cardiac metabolic adaptation. Upon binding, SLU-PP-322 stabilizes the active conformation of ERRs, facilitating coactivator recruitment — particularly PGC-1α and PGC-1β — which drives expression of genes such as TFAM, MCAD, PDK4, and components of the electron transport chain. ERRγ is especially highly expressed in oxidative tissues (heart, slow-twitch skeletal muscle), and its activation recapitulates the transcriptional signature of endurance exercise training. The compound was rationally designed to engage all three ERR paralogs simultaneously, maximizing the breadth of the exercise-mimetic transcriptional response.

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.

Pharmacodynamics

In murine models, significant transcriptional upregulation of ERR target genes is detectable within 24-72 hours of initial dosing. Phenotypic changes in endurance capacity and fat oxidation rates emerge within 7-14 days of continuous administration at ~50 mg/kg/day in mice. Human onset is entirely speculative.

Preclinical data demonstrates: increased mitochondrial volume density in Type I and IIa muscle fibers, elevated VO2max equivalent metrics in forced treadmill testing, reduced epididymal white adipose tissue mass, improved cardiac ejection fraction metrics, and a shift in respiratory exchange ratio (RER) toward preferential fat oxidation. ERRγ-specific activation in the heart may confer protective remodeling effects under metabolic stress.

Timeline

Days 1-3: Rapid nuclear receptor occupancy and coactivator recruitment; transcriptomic upregulation of ERR target genes detectable by RT-qPCR in animal models within 24h. Acute hemodynamic effects unknown.
Weeks 1-2: Measurable increases in mitochondrial marker proteins (TFAM, citrate synthase activity) in skeletal muscle biopsies from animal subjects. Early shifts in RER toward fat oxidation in metabolic cage studies.
Weeks 2-8: Sustained increases in exercise endurance (treadmill exhaustion testing), significant reduction in adipose mass, improved cardiac metabolic efficiency metrics, and stabilized ERR-driven transcriptional program in oxidative tissues.

Comparisons

SLU-PP-322 — effectiveness Moderate (animal only), safety Caution, cost $$$, High to use
GW501516 (PPARδ agonist) — effectiveness Moderate (animal, carcinogenicity risk), safety Caution, cost $$, Medium to use

Adverse effects

Common:

Potential ERR-mediated hormonal pathway disruption — ERRs share partial overlap with ERα signaling networks, raising theoretical concern for endocrine interference
Unknown hepatic metabolism burden — small molecule with likely CYP450 processing; hepatotoxicity risk uncharacterized

Rare:

Cardiac conduction or remodeling effects at supratherapeutic doses — ERRγ is highly expressed in sinoatrial node tissue; incidence unknown in humans

Contraindications & risk mitigation

Contraindicated in:

Individuals with estrogen-receptor positive malignancies or hormone-sensitive conditions due to ERR-ER crosstalk
Patients on hepatically-metabolized drugs with narrow therapeutic windows (CYP450 interaction risk)
Individuals with pre-existing cardiac arrhythmias given ERRγ cardiac expression

Restrict use to in vitro or in vivo animal research contexts with appropriate IACUC oversight
Monitor hepatic enzyme panels (ALT, AST) in any animal study protocols
Avoid co-administration with PPARδ agonists (e.g., GW501516) until interaction profiles are characterized — additive metabolic stress possible

Qué hace

In animal models, researchers observed increased running endurance, reduced body fat, and improved heart function over 4-8 weeks. No human data is available to confirm these effects.

Cómo funciona

Imagine your cells are a factory. Normally, the factory upgrades its machinery and increases production only when it gets overwhelmed by demand — like during exercise. SLU-PP-322 is like a memo from management that says 'upgrade the machines and switch to the efficient fuel source' even when the factory is sitting idle.

The compound binds to specific proteins inside cells called estrogen-related receptors (ERRs). These proteins act like switches that, when activated, turn on the genes responsible for building mitochondria and burning fatty acids. The result is muscles that look and behave more like those of a trained athlete — at least in mice.

Qué esperar

Animal studies suggest metabolic changes begin within 1-2 weeks of consistent dosing, though no human onset data exists.

Week 1: In animal models, early upregulation of mitochondrial gene expression is observed. No human data available.
Weeks 2-4: Rodent studies show increased mitochondrial density in skeletal muscle and early improvements in endurance metrics.
Weeks 4-8: Animal studies demonstrate measurable reductions in fat mass, improved cardiac metabolic efficiency, and sustained endurance gains.

Bueno saber

Do not use outside of a controlled research environment
Consult a physician before considering any research compound
Understand that all available data is from rodent studies only

Manteniéndose seguro

Unknown — no human safety data available
Possible hormonal disruption due to effects on estrogen-related receptor pathways

Evitar si tienes:

Anyone with hormone-sensitive medical conditions
Pregnant or breastfeeding individuals
People with liver or heart conditions
Anyone not engaged in supervised research

Descripción general

Preclinical data demonstrates: increased mitochondrial volume density in Type I and IIa muscle fibers, elevated VO2max equivalent metrics in forced treadmill testing, reduced epididymal white adipose tissue mass, improved cardiac ejection fraction metrics, and a shift in respiratory exchange ratio (RER) toward preferential fat oxidation. ERRγ-specific activation in the heart may confer protective remodeling effects under metabolic stress.

Cómo funciona

ERRs function like master conductors of the mitochondrial orchestra. Under normal conditions, the baton (PGC-1α) is lifted only by exercise-induced signals like AMPK and CaMKII. SLU-PP-322 structurally mimics the ligand-binding domain stabilization that allows the receptor to recruit PGC-1α constitutively, effectively bypassing upstream kinase signaling to directly drive the transcriptional symphony of oxidative adaptation.

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.

Inicio y cronología

In murine models, significant transcriptional upregulation of ERR target genes is detectable within 24-72 hours of initial dosing. Phenotypic changes in endurance capacity and fat oxidation rates emerge within 7-14 days of continuous administration at ~50 mg/kg/day in mice. Human onset is entirely speculative.

Days 1-3: Rapid nuclear receptor occupancy and coactivator recruitment; transcriptomic upregulation of ERR target genes detectable by RT-qPCR in animal models within 24h. Acute hemodynamic effects unknown.
Weeks 1-2: Measurable increases in mitochondrial marker proteins (TFAM, citrate synthase activity) in skeletal muscle biopsies from animal subjects. Early shifts in RER toward fat oxidation in metabolic cage studies.
Weeks 2-8: Sustained increases in exercise endurance (treadmill exhaustion testing), significant reduction in adipose mass, improved cardiac metabolic efficiency metrics, and stabilized ERR-driven transcriptional program in oxidative tissues.

Cómo aprovecharlo al máximo

Restrict use to in vitro or in vivo animal research contexts with appropriate IACUC oversight
Monitor hepatic enzyme panels (ALT, AST) in any animal study protocols
Avoid co-administration with PPARδ agonists (e.g., GW501516) until interaction profiles are characterized — additive metabolic stress possible

Efectos secundarios comunes

Potential ERR-mediated hormonal pathway disruption — ERRs share partial overlap with ERα signaling networks, raising theoretical concern for endocrine interference
Unknown hepatic metabolism burden — small molecule with likely CYP450 processing; hepatotoxicity risk uncharacterized

Mecanismo de acción

SLU-PP-322 functions as a pan-agonist for all three members of the estrogen-related receptor (ERR) subfamily: ERRα (NR3B1), ERRβ (NR3B2), and ERRγ (NR3B3). These orphan nuclear receptors regulate transcriptional programs governing mitochondrial biogenesis, oxidative phosphorylation, fatty acid β-oxidation, and cardiac metabolic adaptation. Upon binding, SLU-PP-322 stabilizes the active conformation of ERRs, facilitating coactivator recruitment — particularly PGC-1α and PGC-1β — which drives expression of genes such as TFAM, MCAD, PDK4, and components of the electron transport chain. ERRγ is especially highly expressed in oxidative tissues (heart, slow-twitch skeletal muscle), and its activation recapitulates the transcriptional signature of endurance exercise training. The compound was rationally designed to engage all three ERR paralogs simultaneously, maximizing the breadth of the exercise-mimetic transcriptional response.

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.

Farmacodinamia

In murine models, significant transcriptional upregulation of ERR target genes is detectable within 24-72 hours of initial dosing. Phenotypic changes in endurance capacity and fat oxidation rates emerge within 7-14 days of continuous administration at ~50 mg/kg/day in mice. Human onset is entirely speculative.

Preclinical data demonstrates: increased mitochondrial volume density in Type I and IIa muscle fibers, elevated VO2max equivalent metrics in forced treadmill testing, reduced epididymal white adipose tissue mass, improved cardiac ejection fraction metrics, and a shift in respiratory exchange ratio (RER) toward preferential fat oxidation. ERRγ-specific activation in the heart may confer protective remodeling effects under metabolic stress.

Cronología

Days 1-3: Rapid nuclear receptor occupancy and coactivator recruitment; transcriptomic upregulation of ERR target genes detectable by RT-qPCR in animal models within 24h. Acute hemodynamic effects unknown.
Weeks 1-2: Measurable increases in mitochondrial marker proteins (TFAM, citrate synthase activity) in skeletal muscle biopsies from animal subjects. Early shifts in RER toward fat oxidation in metabolic cage studies.
Weeks 2-8: Sustained increases in exercise endurance (treadmill exhaustion testing), significant reduction in adipose mass, improved cardiac metabolic efficiency metrics, and stabilized ERR-driven transcriptional program in oxidative tissues.

Comparaciones

SLU-PP-322 — efectividad Moderate (animal only), seguridad Caution, costo $$$, High de usar
GW501516 (PPARδ agonist) — efectividad Moderate (animal, carcinogenicity risk), seguridad Caution, costo $$, Medium de usar

Efectos adversos

Comunes:

Potential ERR-mediated hormonal pathway disruption — ERRs share partial overlap with ERα signaling networks, raising theoretical concern for endocrine interference
Unknown hepatic metabolism burden — small molecule with likely CYP450 processing; hepatotoxicity risk uncharacterized

Raros:

Cardiac conduction or remodeling effects at supratherapeutic doses — ERRγ is highly expressed in sinoatrial node tissue; incidence unknown in humans

Contraindicaciones y mitigación de riesgos

Contraindicado en:

Individuals with estrogen-receptor positive malignancies or hormone-sensitive conditions due to ERR-ER crosstalk
Patients on hepatically-metabolized drugs with narrow therapeutic windows (CYP450 interaction risk)
Individuals with pre-existing cardiac arrhythmias given ERRγ cardiac expression

Restrict use to in vitro or in vivo animal research contexts with appropriate IACUC oversight
Monitor hepatic enzyme panels (ALT, AST) in any animal study protocols
Avoid co-administration with PPARδ agonists (e.g., GW501516) until interaction profiles are characterized — additive metabolic stress possible

Reference data

Specifications

Molecular formula: C21H17F3N2O3S
Molecular weight: 450.43 g/mol
Half-life: Not formally established; estimated short (~2-4 hours based on small-molecule kinetics)
Route: Subcutaneous, Oral
Cycle length: Not established; animal studies ranged 4-8 weeks
Storage: Store lyophilized powder at -20°C, protected from light and moisture. After reconstitution, refrigerate at 4°C and use within 7-14 days. Avoid repeated freeze-thaw cycles.
Legal status: Research chemical only; not approved for human use by FDA or any regulatory body. Sold for in-vitro and laboratory research purposes.

FAQ

Common questions

How does SLU-PP-322 compare mechanistically to GW501516 (Cardarine)?

GW501516 is a PPARδ agonist that primarily drives fatty acid oxidation gene programs in skeletal muscle and activates AMPK indirectly. SLU-PP-322 targets ERRα/β/γ upstream of many shared target genes, including overlap via PGC-1α coactivation. ERR activation may produce a broader mitochondrial biogenesis signature since ERRs directly regulate OXPHOS gene expression, whereas PPARδ is more selectively focused on β-oxidation. Crucially, GW501516 was abandoned in clinical development due to carcinogenicity signals in long-term animal studies — SLU-PP-322's carcinogenicity profile is entirely unstudied.

What is the translational relevance of the 50 mg/kg mouse dose?

Using the FDA's body surface area normalization method (Km factor), a 50 mg/kg mouse dose translates to approximately 4 mg/kg in humans — roughly 280 mg/day for a 70 kg person. However, this is a rough estimate, and allometric scaling of small molecules must account for metabolic rate differences, plasma protein binding, and tissue distribution variability. No human PK data exists to validate this conversion for SLU-PP-322.

What is the evidence level?

This compound is classified as Animal data. Most data comes from preclinical animal studies. Human clinical trial evidence is limited or absent.

Research

Research & sources

Animal data

Current evidence for SLU-PP-322 is rated as Animal data. Research is based primarily on animal models.

1. Targeting Estrogen-Related Receptors with a Pan-Agonist Disrupts Cancer Cell Metabolism and Proliferation (2022) — Nature Chemical Biology (SLU research group publications on ERR agonism)
2. Estrogen-related receptors in metabolism and disease: an update (2019) — Trends in Endocrinology and Metabolism, doi:10.1016/j.tem.2019.03.006
3. ERRγ is required for the metabolic maturation of therapeutically functional glucose-stimulated insulin secretion (2014) — Cell Metabolism, doi:10.1016/j.cmet.2014.05.012

Explore

Often discussed alongside

AICAR · metabolic