Using a Quantitative High-Throughput Screening Platform to Identify Molecular Targets and Compounds as Repurposing Candidates for Endometriosis
Details
Publication Year 2023-06-08,Volume 13,Issue #6,Page 965
Journal Title
Biomolecules
Publication Type
Research article
Abstract
Endometriosis, defined as the growth of hormonally responsive endometrial-like tissue outside of the uterine cavity, is an estrogen-dependent, chronic, pro-inflammatory disease that affects up to 11.4% of women of reproductive age and gender-diverse people with a uterus. At present, there is no long-term cure, and the identification of new therapies that provide a high level of efficacy and favourable long-term safety profiles with rapid clinical access are a priority. In this study, quantitative high-throughput compound screens of 3517 clinically approved compounds were performed on patient-derived immortalized human endometrial stromal cell lines. Following assay optimization and compound criteria selection, a high-throughput screening protocol was developed to enable the identification of compounds that interfered with estrogen-stimulated cell growth. From these screens, 23 novel compounds were identified, in addition to their molecular targets and in silico cell-signalling pathways, which included the neuroactive ligand-receptor interaction pathway, metabolic pathways, and cancer-associated pathways. This study demonstrates for the first time the feasibility of performing large compound screens for the identification of new translatable therapeutics and the improved characterization of endometriosis molecular pathophysiology. Further investigation of the molecular targets identified herein will help uncover new mechanisms involved in the establishment, symptomology, and progression of endometriosis.
Publisher
MDPI
Keywords
Humans; Female; *Endometriosis/drug therapy/metabolism; High-Throughput Screening Assays; Estrogens/metabolism; Endometrium/metabolism; Uterus; endometrial stromal cells; endometriosis; estrogen-signalling pathways; high-content imaging; high-throughput screening
Department(s)
Laboratory Research
PubMed ID
37371546
Open Access at Publisher's Site
https://doi.org/10.3390/biom13060965
Terms of Use/Rights Notice
Refer to copyright notice on published article.


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Last Modified: 2023-09-12 07:44:44

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