An extensive guide to SLU-PP-332: The new exercise mimetic

Imagine getting the benefits of exercise—better endurance, enhanced metabolism, and improved fat-burning—without ever picking up a dumbbell or lacing up your running shoes. While that might sound like science fiction, researchers at Saint Louis University have identified a compound that moves us closer to that reality.

Meet SLU-PP-332, a novel compound that mimics the metabolic effects of exercise by activating energy-regulating receptors in the body. While still in the early stages of research, this molecule is quickly gaining attention in the fields of metabolism, aging, and performance enhancement.

Let’s unpack what it is, how it works, and why it could matter in the years to come.

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What is SLU-PP-332?

SLU-PP-332 is a synthetic small molecule developed by researchers at Saint Louis University (SLU). It functions as an agonist of Estrogen-Related Receptors alpha and gamma (ERRα and ERRγ)—two nuclear receptors that play critical roles in mitochondrial biogenesis, oxidative metabolism, and overall energy expenditure.

It’s important not to confuse SLU-PP-332 with other so-called exercise mimetics like SR9009 (a REV-ERB agonist) or GW501516 (a PPARδ agonist). Unlike those compounds, SLU-PP-332 targets a completely different pathway. By activating ERRα/γ, it directly influences genes responsible for energy production, muscle function, and fat metabolism—all central features of an “exercise-like” response.

How Does SLU-PP-332 Work?

The Estrogen-Related Receptors (ERRs) are orphan nuclear receptors, meaning their natural ligands (if any exist) have not been definitively identified. Despite their name, they don’t bind estrogen. Instead, they regulate energy metabolism in tissues like the heart, skeletal muscle, and brown fat—all organs with high energy demands.

SLU-PP-332 works by binding to ERRα and ERRγ, boosting the transcription of genes involved in:

• Mitochondrial biogenesis
• Fatty acid oxidation
• Oxidative phosphorylation
• Glucose uptake and utilization

In other words, it tells your body to act like it’s in a state of regular aerobic training, even when you’re sitting still.

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Key Findings from the 2023 Study

In a landmark 2023 study led by researchers at SLU, the effects of SLU-PP-332 were tested in sedentary mice over several weeks. Here’s what they found:

• 🏃‍♂️ Endurance Boost: Mice treated with SLU-PP-332 could run significantly longer on a treadmill compared to untreated controls, despite not undergoing any physical training.
• 🔋 Mitochondrial Gene Expression: The compound upregulated genes associated with energy metabolism in skeletal muscle, mimicking the transcriptional signature seen in exercised animals.
• 🔥 Fat Utilization: There was an increase in lipid metabolism, suggesting that the mice were burning more fat as fuel.
• 🧬 No Cardiac Hypertrophy: Unlike some other metabolic enhancers (like GW501516), SLU-PP-332 did not appear to cause adverse heart remodeling, a positive sign for safety.

These results have led some to describe SLU-PP-332 as a “molecular shortcut to fitness”—though that phrase comes with some caveats, which we’ll discuss below.

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SLU-PP-332 vs. Other Exercise Mimetics

There are several compounds that attempt to mimic or enhance the effects of exercise through pharmacology. How does SLU-PP-332 compare?

Compound	Target	Main Effect
SLU-PP-332	ERRα / ERRγ	Mitochondrial biogenesis, endurance
SR9009	REV-ERBα	Circadian rhythm, metabolism
GW501516	PPARδ	Fat burning, endurance
AICAR	AMPK	Cellular energy sensor

What makes SLU-PP-332 especially promising is its direct action on genes involved in energy metabolism, without the off-target effects or toxicity profiles that have haunted other mimetics.

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Potential Benefits

While human studies are needed to confirm real-world applications, the preclinical data suggest that SLU-PP-332 may eventually be useful for:

1. Improving Endurance
   Even in the absence of training, the compound increases mitochondrial function and aerobic capacity in muscle tissue.
2. Treating Metabolic Disorders
   Disorders like obesity, type 2 diabetes, and fatty liver disease might benefit from enhanced mitochondrial activity and improved fat oxidation.
3. Combating Muscle Wasting
   In conditions like aging, cancer cachexia, or long-term bed rest, SLU-PP-332 might help preserve muscle function and energy metabolism.
4. Longevity and Anti-Aging
   While speculative, anything that improves mitochondrial function is of interest to the longevity community. Since mitochondrial decline is linked to aging, boosting their performance could be a powerful intervention.

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Side effects

Every compound – especially a novel one – comes with caveats. So what are the potential downsides of SLU-PP-332? Thus far, animal studies have not reported severe side effects or toxicities from SLU-PP-332 at effective doses. Mice treated for weeks showed improvements in health markers without obvious harm. That is encouraging, but it’s far from a guarantee of safety in humans. Here are some considerations and theoretical risks:

Unknown Long-Term Effects: The biggest limitation is simply the lack of long-term human data. It’s unclear how chronic activation of ERRα might affect various organs over years of use. For example, while ERRα activation boosts metabolism (a good thing for performance and fat loss), an overactive metabolic state could potentially stress certain tissues or disrupt hormonal balances in ways we don’t yet understand.

Because there are no human trials on SLU-PP-332, we must rely on anecdotal reports and evidence for possible side effects. There are multiple posts on Reddit as well as other sources with user experiences, which mention a few of those:

• A (slight) increase in body temperature for about 30 minutes after dosing.
• Some level of exhaustion after the initial increase in energy.
• Increased sweating when working out.

None of these potential side effects are shocking, given the method of action associated with SLU-PP-332.

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Who’s Interested in SLU-PP-332?

Despite its early stage, SLU-PP-332 has piqued interest in several circles:

• Academic researchers studying metabolic disorders, exercise biology, and aging.
• Biohackers exploring new frontiers in performance and recovery (albeit prematurely).
• Pharmaceutical developers considering exercise mimetics as tools for treating chronic diseases.
• Athletes and coaches, though use in sport remains speculative and ethically fraught.

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Dosage and administration

Research findings

Since SLU-PP-332 is currently a research compound, there is no standardized “dose” or usage protocol for humans. However, understanding how it’s been used in studies provides some insight. In animal experiments, relatively high doses were required to see the dramatic effects.

A typical regimen in mice was about 50 mg per kilogram of body weight, given twice daily over several weeks. For a 70 kg (154 lb) human, an equivalent scaled dose would be extremely large (several grams per day) – far beyond what anyone would practically take. It’s likely that if SLU-PP-332 ever progresses to human trials, the effective doses will be much smaller, given differences in metabolism and the compound’s high potency at its target (it activates ERRα at nanomolar concentrations)

In terms of administration, early studies often delivered SLU-PP-332 via injection. For example, research teams reported injecting the compound into mice (intraperitoneally) to ensure consistent absorption. The developers have noted a need to refine the compound into an oral pill form, since an easy-to-take pill would be preferable for human use.

There is good news on that front: SLU-PP-332 appears to have a very decent oral bioavailability (~45%) in rodent models, meaning nearly half of an oral dose can reach the bloodstream – a sign that oral dosing could be viable. In the same study, it was determined that this compound’s half-life is around 8–10 hours in rodents, so future users might expect a twice-daily dosing schedule to maintain steady levels.

Anecdotal reports

As we mentioned before, there have not been any human trials on SLU-PP-332 yet. However, there are many user reports on this compound on Reddit, YouTube, and various message boards. These anecdotal reports shed light on self-experimentation practices.

Dosage Practices

Users report a wide range of dosages, often measured in micrograms (mcg):

• Low Doses (200–500 mcg/day): Some individuals start with 200 mcg in the morning and an additional 200 mcg before afternoon workouts. This regimen is noted for enhancing endurance and energy levels without significant side effects.
• Moderate Doses (500–1,000 mcg/day): Others increase to 500 mcg twice daily, observing consistent fat loss and elevated body temperature. However, some report sleep disturbances at these levels.
• High Doses (1,000–2,000 mcg/day): A subset of users experiment with doses up to 2,000 mcg daily, often split between morning and evening. These individuals report pronounced effects on fat metabolism and energy but also caution about potential overstimulation.

Reported benefits

Anecdotal experiences suggest several potential benefits:

• Increased Energy: Elevated energy levels and reduced perceived exertion during workouts are commonly mentioned.
• Enhanced Endurance: Users note improved stamina during cardiovascular and resistance training sessions.
• Fat Loss: Some report accelerated fat reduction, particularly when combined with calorie-controlled diets.

Reported side effects

Based on the same user reports, there are a couple of side effects reported:

• Increased sweating
• Insomnia (especially at higher dosages)

Frequently asked questions

References

• Billon, C., et al. (2023). “A Synthetic ERR Agonist Alleviates Metabolic Syndrome.” Journal of Pharmacology and Experimental Therapeutics.
• Billon, C., et al. (2022). “Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Program.” ACS Chemical Biology.
• Nasri, H. (2024). “New hopes on ‘SLU-PP-332’ as an effective agent for weight loss with indirect kidney protection efficacy; a nephrology point of view.” Journal of Renal Endocrinology.
• Elgendy, B., et al. (2024). “An exercise pill may soon offer the same benefits as a workout.” Fortune Well.