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Metabolic Modulators

SLU-PP-332

Experimental 'exercise mimetic' that switches on mitochondrial energy genes in mice; no human studies yet.

RestrictedEvidence level 1 of 5: Preclinical / anecdotalAlso: SLU-PP332, ERR agonist SLU-PP-332

Overview

SLU-PP-332 is a small molecule, often mislabeled as a peptide, that activates estrogen-related receptors (ERRs), especially ERRα. Despite the name, these receptors do not respond to estrogen; together with the coactivator PGC-1α, they control the genes that build mitochondria and burn fat. In mice, SLU-PP-332 produced a muscle gene profile resembling endurance training, increased running endurance, raised energy expenditure and reduced fat mass in obese animals. These are encouraging but very early findings from small animal studies. No human trials have been done, and it is poorly water-soluble with low oral bioavailability. Any use in people is experimental.

Classification
Synthetic small-molecule pan-estrogen-related receptor (ERRα/β/γ) agonist; not a peptide
Route
Injected in animal studies; human route not established
Half-life
Not well established

Mechanism of action

Primary targetEstrogen-related receptors (ERRα, with ERRβ/γ)
  1. Binds ERRαActivates the orphan nuclear receptor ERRα in muscle, heart and liver.
  2. Partners with PGC-1αERRα–PGC-1α complex drives mitochondrial gene transcription.
  3. Mitochondrial biogenesisBuilds new mitochondria and electron-transport machinery.
  4. Fatty acid oxidationShifts muscle toward oxidative, fat-burning metabolism.
  5. Exercise-like gene programMuscle expression profile resembles aerobic endurance training.
Downstream effects
  • Greater endurance (mice)
  • Higher energy expenditure
  • Fat-mass reduction (mice)

Researched for

  • Obesity (preclinical)
  • Exercise mimetics
  • Insulin resistance (preclinical)
  • Heart failure (preclinical)
  • Age-related metabolic decline

Research notes

  • Billon 2023 (ACS Chem Biol): mice ran ~70% longer and showed an ERRα-dependent exercise-like muscle gene profile.
  • Billon 2024 (J Pharmacol Exp Ther): obese mice gained less fat and had improved insulin sensitivity; lean mice showed no glucose benefit.
  • Animal doses were injected (intraperitoneal); human dose, route and safety are unknown.
  • Long-term activation of ERR pathways has not been evaluated for cardiac or cancer safety.

Reported side effects

  • Unknown in humans
  • Injection-site irritation (vehicle-related, anecdotal)
  • Potential vehicle (DMSO) effects

Contraindications & cautions

  • Pregnancy or breastfeeding
  • Active malignancy
  • Significant heart, liver or kidney disease
  • Competitive athletes (anti-doping surveillance)

Lab monitoring

  • CMP with liver enzymes
  • CBC
  • Fasting glucose, HbA1c, fasting insulin
  • Lipid panel

Dosing and pricing for SLU-PP-332

Dosing references and compound pricing are available to established patients in the secure portal after a medical evaluation.

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