Description

SLU-PP-332 Peptide

SLU-PP-332 is a synthetic compound investigated for its activity as a REV-ERBα/β agonist, a nuclear receptor pathway implicated in circadian rhythm regulation, metabolic homeostasis, and mitochondrial function. This peptide-based research molecule is part of a novel class of compounds that selectively target REV-ERB nuclear hormone receptors, which are key transcriptional repressors modulating clock gene expression and cellular metabolism.

Experimental studies have suggested that SLU-PP-332 may mimic the action of endogenous ligands like heme, which naturally bind to REV-ERB receptors. By enhancing the repressive activity of REV-ERBα/β, SLU-PP-332 is being investigated for its potential to influence energy expenditure, glucose and lipid metabolism, and inflammatory responses. Research indicates a promising role in models of obesity, metabolic syndrome, and neurodegenerative conditions associated with circadian disruption.

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Chemical Makeup

• Molecular Formula: C30H35N5O3

• Molecular Weight: 513.63 g/mol

• Mechanism of Action: REV-ERBα/β receptor agonist

• Solubility: DMSO, ethanol

• Structure Type: Non-peptidic small molecule

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Research & Preclinical Investigations

SLU-PP-332 and Circadian Regulation

REV-ERBs are core components of the molecular circadian clock. SLU-PP-332 has demonstrated the ability to suppress transcription of circadian genes such as BMAL1, NPAS2, and Clock, resulting in altered oscillatory behavior in experimental circadian rhythm models. In vitro data show time-dependent gene silencing consistent with enhanced REV-ERB signaling.

Mitochondrial Biogenesis and Metabolic Modulation

Studies in murine models suggest that SLU-PP-332 may promote mitochondrial respiration by upregulating genes associated with oxidative phosphorylation and fatty acid oxidation. Research points to enhanced expression of PGC-1α, UCP1, and CPT1B—critical components of mitochondrial metabolism—particularly in brown adipose tissue and skeletal muscle.

Anti-Inflammatory and Neuroprotective Potential

Preclinical models have also explored SLU-PP-332 for its effects on neuroinflammation. By suppressing pro-inflammatory cytokines such as IL-6 and TNF-α, and modulating microglial activity, SLU-PP-332 has shown potential in models of neurodegeneration and systemic inflammation. The compound may support neuronal health by indirectly reducing oxidative stress and supporting metabolic resilience in glial cells.

Pharmacokinetics and Administration

SLU-PP-332 has demonstrated a favorable pharmacokinetic profile in rodent models, with oral bioavailability and a half-life suitable for once-daily dosing in time-restricted protocols. Its activity appears to be dose-dependent and time-of-day sensitive, emphasizing its relevance to chronopharmacological research.

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Research Use Only

SLU-PP-332 is provided for in vitro and in vivo laboratory research use only. It is not intended for human or veterinary use, clinical trials, or diagnostic purposes. All research involving this compound should be conducted under appropriate institutional biosafety regulations.

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References

1. Solt LA, Wang Y, Banerjee S, et al. Regulation of circadian behavior and metabolism by synthetic REV-ERB agonists. Nature. 2012;485(7396):62–68.

2. Kojetin DJ, Burris TP. REV-ERB and ROR nuclear receptors as drug targets. Nat Rev Drug Discov. 2014;13(3):197–216.

3. Griffin P, Dimitry JM, Sheehan PW, et al. Circadian clock protein Rev-erbα regulates neuroinflammation. Proc Natl Acad Sci USA. 2019;116(11):5102–5107.

4. Zhang Y, Fang B, Emmett MJ, et al. GENE REGULATION. Discrete functions of nuclear receptor Rev-erbα couple metabolism to the clock. Science. 2015;348(6242):1488–1492.