SLU-PP-332
A compound developed at Washington University that activates estrogen-related receptor alpha. A next-generation exercise mimetic that enhances endurance and promotes slow-twitch muscle fiber transformation through a different mechanism than AICAR. Activates the same gene programs that endurance training induces, including mitochondrial growth and fat-burning metabolism.
Dosage
Preclinical only — no established human dosing
Dosages shown are for research reference only. Always consult a qualified healthcare provider.
Administration
Oral or injection (preclinical only)
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Effects
Endurance Enhancement
Shifts muscle fiber composition toward fatigue-resistant slow-twitch type.
Mitochondrial Biogenesis
ERRalpha activation upregulates entire oxidative metabolism gene program.
Mechanism of Action
SLU-PP-332 is a small molecule agonist of estrogen-related receptor alpha (ERRα), one of three orphan nuclear receptors in the ERR family. Despite its name, ERRα does not bind estrogen — it was named for its structural similarity to estrogen receptors. ERRα is constitutively active and functions as a master transcription factor for genes controlling mitochondrial biogenesis, oxidative phosphorylation, and fatty acid oxidation, particularly in metabolically active tissues like skeletal muscle, heart, and brown adipose tissue.
SLU-PP-332 enhances ERRα transcriptional activity by stabilizing its active conformation and promoting coactivator recruitment (particularly PGC-1α, which is both an ERRα target gene and an ERRα coactivator, creating a positive feed-forward loop). Activated ERRα binds to ERR response elements (ERREs) in the promoter regions of hundreds of metabolic genes, upregulating the entire oxidative metabolism gene program: mitochondrial electron transport chain subunits, fatty acid oxidation enzymes, TCA cycle enzymes, and mitochondrial transcription and replication factors.
The most striking effect in preclinical studies is the transformation of skeletal muscle fiber type composition. SLU-PP-332 treatment increases the proportion of slow-twitch (type I) and oxidative fast-twitch (type IIA) fibers while decreasing glycolytic fast-twitch (type IIB/IIX) fibers. Type I fibers are rich in mitochondria, capillaries, and myoglobin — they are the fibers that endurance athletes develop through years of training. By pharmacologically shifting this fiber type ratio, SLU-PP-332 produces endurance capacity gains similar to what would require months of aerobic training. In mouse studies published in 2023, treated animals ran significantly longer and farther on treadmill tests. This ERRα-mediated mechanism is distinct from and potentially complementary to AMPK-based exercise mimetics like AICAR, as it targets a different node in the mitochondrial biogenesis regulatory network.
Regulatory Status
Not FDA approved. Preclinical research compound. Published in 2023 by Washington University. No clinical trials. Available through research chemical suppliers.
Risks & Safety
Serious
no human safety data exists, potential off-target effects on estrogen-responsive tissues and metabolic pathways are entirely unstudied.
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Research Papers
1Published: December 16, 2023
AI Summary
Eight weeks of SLU-PP-332 treatment reversed age-related kidney changes in elderly mice, including albuminuria, podocyte loss, mitochondrial dysfunction, and inflammation. The pan-ERR agonist acted like caloric restriction, highlighting a potential druggable pathway for age-related kidney disease.
Frequently Asked Questions
What is SLU-PP-332?
A compound developed at Washington University that activates estrogen-related receptor alpha. A next-generation exercise mimetic that enhances endurance and promotes slow-twitch muscle fiber transformation through a different mechanism than AICAR. Activates the same gene programs that endurance training induces, including mitochondrial growth and fat-burning metabolism.
What is SLU-PP-332 used for?
A compound developed at Washington University that activates estrogen-related receptor alpha. A next-generation exercise mimetic that enhances endurance and promotes slow-twitch muscle fiber transformation through a different mechanism than AICAR. Activates the same gene programs that endurance training induces, including mitochondrial growth and fat-burning metabolism.
What is the dosage for SLU-PP-332?
Preclinical only: mouse studies used 25-50 mg/kg oral. No established human dosing protocol. Very early stage compound with no human trials conducted.
What are the side effects of SLU-PP-332?
Serious: no human safety data exists, potential off-target effects on estrogen-responsive tissues and metabolic pathways are entirely unstudied.
How does SLU-PP-332 work?
SLU-PP-332 is a small molecule agonist of estrogen-related receptor alpha (ERRα), one of three orphan nuclear receptors in the ERR family. Despite its name, ERRα does not bind estrogen — it was named for its structural similarity to estrogen receptors. ERRα is constitutively active and functions as a master transcription factor for genes controlling mitochondrial biogenesis, oxidative phosphorylation, and fatty acid oxidation, particularly in metabolically active tissues like skeletal muscle, heart, and brown adipose tissue. SLU-PP-332 enhances ERRα transcriptional activity by stabilizing its active conformation and promoting coactivator recruitment (particularly PGC-1α, which is both an ERRα target gene and an ERRα coactivator, creating a positive feed-forward loop). Activated ERRα binds to ERR response elements (ERREs) in the promoter regions of hundreds of metabolic genes, upregulating the entire oxidative metabolism gene program: mitochondrial electron transport chain subunits, fatty acid oxidation enzymes, TCA cycle enzymes, and mitochondrial transcription and replication factors. The most striking effect in preclinical studies is the transformation of skeletal muscle fiber type composition. SLU-PP-332 treatment increases the proportion of slow-twitch (type I) and oxidative fast-twitch (type IIA) fibers while decreasing glycolytic fast-twitch (type IIB/IIX) fibers. Type I fibers are rich in mitochondria, capillaries, and myoglobin — they are the fibers that endurance athletes develop through years of training. By pharmacologically shifting this fiber type ratio, SLU-PP-332 produces endurance capacity gains similar to what would require months of aerobic training. In mouse studies published in 2023, treated animals ran significantly longer and farther on treadmill tests. This ERRα-mediated mechanism is distinct from and potentially complementary to AMPK-based exercise mimetics like AICAR, as it targets a different node in the mitochondrial biogenesis regulatory network.
How is SLU-PP-332 administered?
SLU-PP-332 is administered via oral or injection (preclinical only).
What is the half-life of SLU-PP-332?
The half-life of SLU-PP-332 is Estimated several hours (limited pharmacokinetic data).
Is SLU-PP-332 legal?
Not FDA approved. Preclinical research compound. Published in 2023 by Washington University. No clinical trials. Available through research chemical suppliers.
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