SLU-PP-332: Is it really an exercise mimetic?

by Andrew Berry on March 31, 2025

What is SLU-PP-332?

SLU-PP-332 is a synthetic compound that functions as a pan-agonist (a drug or compound that activates multiple subtypes of a specific receptor) for estrogen receptor-related receptors (ERRs), particularly ERRα. It has been shown to enhance mitochondrial function and respiration in skeletal muscle cells, effectively mimicking the same effects one would get from physical exercise. This has made it a promising candidate for therapeutic interventions in metabolic diseases, muscle disorders and of course physique enhancement.

How Does SLU-PP-332 Work?

SLU-PP-332 is a pan-agonist of the estrogen-related receptor (ERR) family—specifically ERRα, ERRβ, and ERRγ. While these receptors aren’t related to testosterone or estrogen directly, they play a huge role in energy metabolism, mitochondrial efficiency, and endurance performance. By activating ERRα, SLU-PP-332 increases the expression of genes responsible for fatty acid oxidation and mitochondrial biogenesis—the same adaptations seen with high-intensity endurance training. In skeletal muscle cells, it shifts fiber composition toward oxidative (Type I and Type IIa) fibers, meaning greater endurance and more efficient ATP production. (Billon et al., 2023)

Some Science
In a paper published in ACS Chemical Biology, Billion and colleagues reported that mice dosed with SLU-PP-332 boosted the activity of ERRs and in observation these normal-weight mice were able to run 70% longer and 45% further than mice not given the drug. Additionally, his team tested the drug on obese mice twice a day for a month. Despite eating the same diet, they had previously, these mice lost 12% of their bodyweight compared to the controls. (Billon et al., 2023)

Kidney Repair
SLU-PP-33 is also showing promise as a novel therapeutic in kidney and heart disease. According to a study from The American Journal of Pathology in 2023, researchers explored the therapeutic potential of SLU-PP-332 in reversing age-related renal decline in mice. The researchers treated 18-month-old mice (typical life span 26-30 months) with SLU-PP-332 for 8 weeks and assessed its effects on kidney function compared to untreated aged mice and younger (4-month-old) controls. The results demonstrated that SLU-PP-332 significantly reduced age-associated kidney impairments, including lowering albuminuria (a key indicator of kidney damage), preserving podocyte (specialized epithelial cells located in the glomerulus of the kidney) numbers, and decreasing glomerulosclerosis. These improvements were tied to enhanced mitochondrial function and reduced inflammation in the kidneys, mediated through pathways such as cyclic GMP-AMP synthase-STING and STAT3 signaling. The treatment mimicked the protective effects of caloric restriction, suggesting that SLU-PP-332 activates metabolic and cellular repair mechanisms. Beyond the kidneys, the study also noted systemic benefits, such as improved muscle function and metabolic health, indicating broader anti-aging potential. The findings position SLU-PP-332 as a promising exercise-mimetic compound for mitigating age-related renal dysfunction and related comorbidities, warranting further investigation for clinical applications. (Wang et al., 2023)

Heart Protection
In a 2021 study printed in Circulation, Xu and researchers studied the effects of SLU-PP-332 and SLU-PP-91 another ERR agonist in treating heart failure. ERRα and ERRγ play a critical role in cardiac metabolism and mice lacking these receptors develop lethal cardiomyopathy suggesting the ERR activation may be cardioprotective. The researchers tested the two compounds on cardiac function in mice with TAC (transaortic constriction) induced heart failure. After 6 weeks of TAC, both compounds significantly improved ejection fraction, mitochondrial structure, and reduced heart failure markers and fibrosis, though they did not prevent cardiac hypertrophy. In vitro, 332 and 915 failed to block phenylephrine-induced hypertrophy or ERK1/2 and NFAT signaling in NRVMs. The study concludes that SLU-PP-332 and 915, predominantly through ERRγ, improve mitochondrial function and cardiac performance in TAC-induced heart failure, highlighting ERR agonists as promising therapeutic candidates despite their inability to prevent hypertrophy. This is confirmed in a follow up study done by the same researchers in 2024. (Xu et al., 2001) (Xu et al., 2024)

SLU-PP-332 for Fat Loss and Lean Gains

So, we can see the potential health benefits for people with metabolic dysfunction, type 2 diabetes, obesity and those with heart and kidney health issues. Does it have application in bodybuilding?

For bodybuilders, staying in shape without sacrificing muscle mass is the ultimate goal. SLU-PP-332’s ability to upregulate fat oxidation and enhance mitochondrial efficiency could make it a valuable tool for cutting cycles and recomposition.

Potential Benefits for Bodybuilders:

Cut Fat Without Losing Muscle – It enhances fat burning while preserving muscle mass, ideal for contest prep or a lean bulk.
Boost Endurance Without Extra Cardio – Improved muscular efficiency and ATP production means you can lift longer without fatigue.
Increase Nutrient Partitioning – Better insulin sensitivity means more nutrients go to muscle instead of fat storage.

Side Effects?

Right now, we don’t have much data of safety. Animal studies suggest SLU-PP-332 is well-tolerated with no reported toxic effects, but these were only short-term studies and not done on humans.

That said, because ERR activation increases mitochondrial activity, there’s potential for higher energy demands, meaning nutrition must be on point to prevent muscle breakdown.

Authors Anecdote

I have been using SLU-PP-332 for several months now and can report it’s been positive. I have kept cardio, nutrition and training variables the same and while maintaining the same body weight have had a solid recomposition effect with lower body fat levels. I notice cardiovascular work is easier as are higher repetition sets. During the first week, I noticed an increase I appetite which died down in the following weeks. The one thing I have noticed that may or may not be related is that I have had poorer sleep, waking up several times a night much more frequently. Besides that, its been nothing but positive and I plan to continue using as part of my anti-aging/performance regimen.

Andrew is a strength coach and nutritionist in the South Burlington, Vermont area. Andrew has worked with John closely for several years and knows the ins and outs of the Mountain Dog philosophy and is an integral part of the team.