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Updated: Aug 23, 2025

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
Published on: December 11, 2016
Differential Interactome Based Drug Repositioning Unraveled Abacavir, Exemestane, Nortriptyline Hydrochloride, and
Hande Beklen1, Sema Arslan2, Gizem Gulfidan1
1Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey.
Abstract:
There is a critical requirement for alternative strategies to provide the better treatment in colorectal cancer (CRC). Hence, our goal was to propose novel biomarkers as well as drug candidates for its treatment through differential interactome based drug repositioning. Differentially interacting proteins and their modules were identified, and their prognostic power were estimated through survival analyses. Drug repositioning was carried out for significant target proteins, and candidate drugs were analyzed via in silico molecular docking prior to in vitro cell viability assays in CRC cell lines. Six modules (mAPEX1, mCCT7, mHSD17B10, mMYC, mPSMB5, mRAN) were highlighted considering their prognostic performance. Drug repositioning resulted in eight drugs (abacavir, ribociclib, exemestane, voriconazole, nortriptyline hydrochloride, theophylline, bromocriptine mesylate, and tolcapone). Moreover, significant in vitro inhibition profiles were obtained in abacavir, nortriptyline hydrochloride, exemestane, tolcapone, and theophylline (positive control). Our findings may provide new and complementary strategies for the treatment of CRC.
Insights
This study identifies novel biomarkers and drug candidates for colorectal cancer (CRC) treatment using a novel interactome-based drug repositioning strategy. Several drugs showed significant in vitro efficacy, offering new therapeutic avenues for CRC.
Area of Science:
- Oncology
- Bioinformatics
- Pharmacology
Background:
- Colorectal cancer (CRC) necessitates innovative treatment strategies.
- Identifying reliable biomarkers and effective drug candidates is crucial for improving CRC patient outcomes.
Purpose of the Study:
- To propose novel biomarkers and drug candidates for colorectal cancer (CRC) treatment.
- To utilize differential interactome-based drug repositioning for identifying therapeutic targets and drugs.
Main Methods:
- Identification of differentially interacting proteins and modules with prognostic value using survival analyses.
- Drug repositioning targeting significant proteins, followed by in silico molecular docking.
- In vitro validation of candidate drugs using colorectal cancer (CRC) cell lines.
Main Results:
- Six key modules (mAPEX1, mCCT7, mHSD17B10, mMYC, mPSMB5, mRAN) were identified for their prognostic significance.
- Eight potential drugs were repositioned, including abacavir, ribociclib, exemestane, voriconazole, nortriptyline hydrochloride, theophylline, bromocriptine mesylate, and tolcapone.
- Significant in vitro inhibition was observed for abacavir, nortriptyline hydrochloride, exemestane, tolcapone, and theophylline in CRC cell lines.
Conclusions:
- The study presents a novel approach for colorectal cancer (CRC) treatment strategy development.
- Identified biomarkers and repositioned drugs offer potential complementary therapeutic options for CRC.
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