Using a Quantitative High-Throughput Screening Platform to Identify Molecular Targets and Compounds as Repurposing...

Area of Science:

• Reproductive biology
• Pharmacology
• Genitourinary medicine

Background:

• Endometriosis is an estrogen-dependent, chronic, pro-inflammatory disease affecting up to 11.4% of women of reproductive age and gender-diverse people with a uterus.
• Current treatments lack long-term cures, necessitating the urgent discovery of novel, safe, and effective therapies.
• Identifying new therapeutic targets is crucial for improving patient outcomes and understanding disease progression.

Purpose of the Study:

• To conduct high-throughput screening of clinically approved compounds to identify novel therapeutics for endometriosis.
• To investigate molecular targets and signaling pathways involved in endometriosis pathophysiology.
• To establish the feasibility of large-scale compound screening for endometriosis drug discovery.

Main Methods:

• Quantitative high-throughput compound screening of 3,517 clinically approved drugs.
• Utilized patient-derived immortalized human endometrial stromal cell lines.
• Developed and optimized a screening protocol to identify compounds inhibiting estrogen-stimulated cell growth.

Main Results:

• Identified 23 novel compounds that interfere with estrogen-stimulated endometrial cell growth.
• Characterized molecular targets and in silico cell-signaling pathways, including neuroactive ligand-receptor interactions, metabolic pathways, and cancer-associated pathways.
• Demonstrated the feasibility of large-scale compound screening for endometriosis therapeutics.

Conclusions:

• This study successfully identified novel compounds with therapeutic potential for endometriosis.
• The findings highlight the utility of high-throughput screening in drug discovery for complex diseases.
• Further research into identified molecular targets will elucidate endometriosis mechanisms and inform future treatment strategies.