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Updated: Oct 21, 2025
Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
Published on: December 11, 2016
Repurposing new drug candidates and identifying crucial molecules underlying PCOS Pathogenesis Based On
Zeinab Dehghan1,2, Samira Mohammadi-Yeganeh2,3, Marzieh Sameni1,2
1Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Backgrounds:
Polycystic ovary syndrome affects 7% of women of reproductive ages. Poor-quality oocytes, along with lower cleavage and implantation rates, reduce fertilization.
Objective:
This study aimed to determine crucial molecular mechanisms behind PCOS pathogenesis and repurpose new drug candidates interacting with them. To predict a more in-depth insight, we applied a novel bioinformatics approach to analyze interactions between the drug-related and PCOS proteins in PCOS patients.
Methods:
The newest proteomics data was retrieved from 16 proteomics datasets and was used to construct the PCOS PPI network using Cytoscape. The topological network analysis determined hubs and bottlenecks. The MCODE Plugin was used to identify highly connected regions, and the associations between PCOS clusters and drug-related proteins were evaluated using the Chi-squared/Fisher's exact test. The crucial PPI hub-bottlenecks and the shared molecules (between the PCOS clusters and drug-related proteins) were then investigated for their drug-protein interactions with previously US FDA-approved drugs to predict new drug candidates.
Results:
The PI3K/AKT pathway was significantly related to one PCOS subnetwork and most drugs (metformin, letrozole, pioglitazone, and spironolactone); moreover, VEGF, EGF, TGFB1, AGT, AMBP, and RBP4 were identified as the shared proteins between the PCOS subnetwork and the drugs. The shared top biochemical pathways between another PCOS subnetwork and rosiglitazone included metabolic pathways, carbon metabolism, and citrate cycle, while the shared proteins included HSPB1, HSPD1, ACO2, TALDO1, VDAC1, and MDH2. We proposed some new candidate medicines for further PCOS treatment investigations, such as copper and zinc compounds, reteplase, alteplase, gliclazide, Etc.
Conclusion:
Some of the crucial molecules suggested by our model have already been experimentally reported as critical molecules in PCOS pathogenesis. Moreover, some repurposed medications have already shown beneficial effects on infertility treatment. These previous experimental reports confirm our suggestion for investigating our other repurposed drugs (in vitro and in vivo).
Insights
This study identifies key molecular mechanisms in polycystic ovary syndrome (PCOS) and proposes new drug candidates. Bioinformatics analysis revealed shared proteins and pathways, suggesting novel therapeutic targets for PCOS and infertility.
Area of Science:
- Reproductive endocrinology
- Bioinformatics
- Genomics
Background:
- Polycystic ovary syndrome (PCOS) affects 7% of women of reproductive age.
- PCOS is associated with poor oocyte quality, reducing fertilization and implantation rates.
Purpose of the Study:
- To elucidate critical molecular mechanisms in PCOS pathogenesis.
- To identify novel drug candidates for PCOS by analyzing drug-protein interactions.
- To gain in-depth insight using a bioinformatics approach.
Main Methods:
- Constructed a PCOS protein-protein interaction (PPI) network from 16 proteomics datasets.
- Identified key network hubs, bottlenecks, and clusters using Cytoscape and MCODE.
- Evaluated associations between PCOS clusters and drug-related proteins.
- Investigated drug-protein interactions for FDA-approved drugs to predict new candidates.
Main Results:
- The PI3K/AKT pathway was linked to a PCOS subnetwork and drugs like metformin and letrozole.
- Identified shared proteins (e.g., VEGF, EGF) between PCOS subnetworks and drugs.
- Another PCOS subnetwork shared metabolic pathways with rosiglitazone, involving proteins like HSPB1 and HSPD1.
- Proposed candidate drugs including copper/zinc compounds, reteplase, alteplase, and gliclazide.
Conclusions:
- Identified crucial molecules in PCOS pathogenesis, some previously reported.
- Repurposed medications showed potential for PCOS and infertility treatment.
- Previous findings support further in vitro and in vivo investigation of proposed drugs.
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