A transcriptomics-based computational drug repurposing pipeline identifies simvastatin and primaquine as therapeutics for endometriosis

Tomiko Oskotsky, Xinyu Tang, Erin Arthurs, Arpita Govil, Abbasi F, Arohee Bhoja, Daniel Bunis, Abby Lau, Jakob Einhaus, Maïgane Diop, Juan C. Irwin, Brice Gaudilliere, David K. Stevenson, Linda C. Giudice, Stacy L. McAllister, Marina Sirota
In: iScience · 2026 · vol. 29(9) , pp. 117153 · doi:10.1016/j.isci.2026.117153 · W7203942674
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Simvastatin and primaquine attenuated pain and reversed gene expression changes in a rat endometriosis model, while simvastatin prescription was associated with a lower risk of endometriosis in a retrospective human cohort study.

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Abstract

Endometriosis has limited treatment options, prompting the search for data-driven therapeutics. We previously used a transcriptomics-based computational drug repositioning pipeline and identified several drug candidates. Fenoprofen, our top in silico candidate, was validated in a rat model of endometriosis-associated pain. Building on this, we evaluated two additional candidates, simvastatin and primaquine. Using the rat model, we conducted behavioral testing, bulk RNA sequencing, and differential expression analysis to assess their therapeutic potential. We also assessed endometriosis diagnosis among patients prescribed simvastatin in electronic medical records across six University of California (UC) healthcare institutions. Overall, simvastatin and primaquine attenuated pain-associated behaviors and reversed endometriosis-related gene expression changes in our animal model. Moreover, simvastatin prescription was associated with a lower observed relative risk of endometriosis in our retrospective multi-center cohort study. These findings highlight their potential as repurposed therapeutics for endometriosis and support the effectiveness of computational drug repositioning in identifying treatment strategies.

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