SLU-PP-332 and SLU-PP-915 - Estrogen-related receptor (ERR) agonists - Doping ?

New publication
 _{20th January 2026}

Möller T, Krug O, Thevis M. In Vitro Metabolism and Analytical Characterization of SLU-PP-332 and SLU-PP-915: Novel Pan-ERR Agonists With Doping Potential. Rapid Commun Mass Spectrom. 2026 Apr 30;40(8):e70039. doi: 10.1002/rcm.70039. PMID: 41588687; PMCID: PMC12835572.

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Abstract

Rationale: Estrogen-related receptor (ERR) agonists such as the drug candidates SLU-PP-332 and SLU-PP-915 are currently being investigated as exercise mimetics, given their ability to trigger human physiological processes similar to those initiated by actual physical activity. This capability prompted the consideration of these compounds as drugs potentially relevant for sports drug testing programs.

Methods: The two pan-ERR agonists SLU-PP-332 and SLU-PP-915 were characterized using liquid chromatography-high resolution (tandem) mass spectrometry (LC-HRMS/MS). Furthermore, the in vitro metabolic transformation products of both compounds prepared by means of human liver S9 fraction (S9 fraction) and human liver microsomes (HLMs) were analyzed. In addition, selected metabolites of SLU-PP-915 were synthesized and their structures were analyzed by nuclear magnetic resonance (NMR) spectroscopy.

Results: A total of nine metabolites were identified for SLU-PP-332, consisting of six Phase-I metabolites and three Phase-II conjugates. Conversely, the analysis of SLU-PP-915 yielded only Phase-I transformation products, with a total of seven metabolites identified. In both cases, an in-depth structural elucidation was conducted to obtain a comprehensive overview of the detected metabolites. Furthermore, three metabolites of SLU-PP-915 were confirmed through chemical synthesis and NMR.

Conclusion: The results obtained in this study gave an in-depth view into the analysis and in vitro metabolism of the newly developed pan-ERR agonists SLU-PP-332 and SLU-PP-915. This may help to uncover the illicit use of these novel compounds as potential performance-enhancing substances.

Keywords: LC‐HRMS; in vitro metabolism; metabolite synthesis; pan‐ERR agonists.