What it is
SLU-PP-915 is a synthetic small-molecule agonist of all three estrogen-related receptors: ERRα, ERRβ, and ERRγ. These orphan nuclear receptors regulate genes involved in mitochondrial biogenesis, oxidative phosphorylation, fatty-acid oxidation, and cellular energy use. Despite the name, SLU-PP-915 is not estrogen and it is not a peptide.
Why it is different from SLU-PP-332
SLU-PP-915 is not simply an oral formulation of SLU-PP-332. It is a chemically distinct thiophene-based molecule containing a boronic-acid group. The medicinal-chemistry program retained activity across all three ERRs while improving metabolic stability, and later mouse work demonstrated oral systemic exposure and exercise-mimetic activity.
The gene-program rationale
Early cell and mouse experiments found increased expression of ERR target genes including PGC-1α, LDHA, DDIT4, and PDK4. Those genes sit within pathways related to mitochondrial adaptation, fuel use, and the acute response to aerobic exercise. DDIT4 became a central marker in the later performance study because its induction tracked with running time and distance in mice.
The mouse exercise result
In an acute experiment, 20 mg/kg of SLU-PP-915 given by intraperitoneal injection one hour before running increased mouse treadmill time and distance to exhaustion, with performance similar to 50 mg/kg of SLU-PP-332. In seven-day experiments, oral SLU-PP-915 given twice daily increased DDIT4 expression, mitochondrial gene expression, mitochondrial DNA content, and running performance. Exercise and SLU-PP-915 together produced a larger molecular response than either alone.
What the study does not establish
The exercise experiments were conducted in mice, not people. They do not establish a human performance dose, pharmacokinetic profile, safety range, or expected subjective effect. My current 20 mg/day exposure is therefore a personal record rather than a translation of a clinically validated protocol.
The weight-loss hypothesis is secondary
The SLU-PP-915 performance paper did not test human weight loss and was centered on aerobic capacity and skeletal-muscle signaling. The body-composition rationale comes indirectly from ERR control of fatty-acid metabolism and from mouse studies of SLU-PP-332 that reported higher energy expenditure, greater fatty-acid oxidation, and less fat-mass accumulation. That makes weight loss worth observing here, but not the primary claim being tested.
Sources
- Hampton et al., European Journal of Medicinal Chemistry 2023 — discovery, chemical optimization, pan-ERR activity, metabolic stability, and early target-gene experiments for SLU-PP-915.
- Billon et al., Journal of Pharmacology and Experimental Therapeutics 2026 — oral exposure, DDIT4 and mitochondrial responses, and exercise performance in mice.
- Billon et al., ACS Chemical Biology 2023 — foundational SLU-PP-332 work connecting ERR activation with an acute aerobic exercise program and mouse endurance.
- Billon et al., Journal of Pharmacology and Experimental Therapeutics 2024 — metabolic and fat-mass findings for SLU-PP-332 in mouse models of obesity and metabolic syndrome.