Evidence map›Paper›PMID 40502156›Full record

ArticlebioRxiv : the preprint server for biology2025

A Transcriptomics-Based Computational Drug Repositioning Pipeline Identifies Simvastatin And Primaquine As Novel Therapeutics For Endometriosis Pain.

Tomiko T Oskotsky, Xinyu Tang, Erin Arthurs, Arpita Govil, Ferheen Abbasi, Arohee Bhoja, Daniel J Bunis, Abby Lau, Jakob Einhaus, Maïgane Diop and 6 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Tomiko T OskotskyBakar Computational Health Sciences Institute, University of California, San Francisco, CA, USA.ORCID 0000-0001-7393-5120
Xinyu TangBakar Computational Health Sciences Institute, University of California, San Francisco, CA, USA.
Erin ArthursDepartment of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA.
Arpita GovilDepartment of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA.
Ferheen AbbasiCenter for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA.
Arohee BhojaBakar Computational Health Sciences Institute, University of California, San Francisco, CA, USA.
Daniel J BunisBakar Computational Health Sciences Institute, University of California, San Francisco, CA, USA.
Abby LauDepartment of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA.
Jakob EinhausDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA.
Maïgane DiopDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA.ORCID 0000-0003-2580-8084
Juan C IrwinCenter for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA.
Brice GaudilliereDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA.ORCID 0000-0002-3475-5706
David K StevensonDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Linda C GiudiceCenter for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA.ORCID 0000-0002-1677-0822
Stacy L McAllisterDepartment of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA.
Marina SirotaBakar Computational Health Sciences Institute, University of California, San Francisco, CA, USA.ORCID 0000-0002-7246-6083

Funding

Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE)UL1TR002378 · NCATS · EMORY UNIVERSITY · PI Andres J Garcia, Elizabeth O. Ofili · 2017 to 2026
$92.1M
Project 4: Human Endometrial Programming for Successful ImplantationP50HD055764 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MELLON, SYNTHIA H · 2014 to 2022
$16.4M
UCSF Stanford Endometriosis Center for Discovery, Innovation, Training and Community EngagementP01HD106414 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GAUDILLIERE, BRICE, GIUDICE, LINDA C · 2021 to 2025
$7.1M
Targeting Reactive Aldehyde Metabolism in Endometriosis as a treatment strategy and a Diagnostic BiomarkerR00HD093858 · NICHD · EMORY UNIVERSITY · PI MCALLISTER, STACY L · 2019 to 2021
$686k
NCATS NIH HHS UL1 TR002378NICHD NIH HHS P01 HD106414NICHD NIH HHS P50 HD055764NICHD NIH HHS R00 HD093858
6 · The paper itself

Abstract

Introduction and Methods: Endometriosis has limited treatment options, prompting the search for novel therapeutics. We previously used a transcriptomics-based computational drug repositioning pipeline to analyze public bulk transcriptomic data and identified several drug candidates. Fenoprofen, our top in silico candidate, was validated in a rat model. Building on this, we now evaluate two additional candidates, simvastatin (a cholesterol-lowering drug) and primaquine (an antimalarial), based on strong gene expression reversal scores and favorable safety profiles. Using a validated rat model of endometriosis and pain, we conducted behavioral testing, bulk RNA sequencing, and differential expression analysis to assess their therapeutic potential. Results: Of 299 drugs identified computationally, simvastatin and primaquine ranked highly for reversing gene expression signatures associated with endometriosis. In vivo validation using a rat model of endometriosis demonstrated that both drugs significantly reduced vaginal hyperalgesia, a surrogate marker of endometriosis-associated pain. RNA-seq of uteri and lesions confirmed reversal of disease-associated gene expression signatures following treatment. Conclusion: Simvastatin and primaquine attenuated pain behaviors and reversed endometriosis-related gene expression changes in an animal model. These findings highlight their potential as repurposed therapeutics for endometriosis-related pain and support the effectiveness of computational drug repositioning strategies in identifying new treatment strategies.

Indexed as

bioinformaticsdrug repositioningendometriosistherapeuticstranscriptomics

Identifiers

PMID40502156
PMCPMC12154721

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.