Differential Interactome Based Drug Repositioning Unraveled Abacavir, Exemestane, Nortriptyline Hydrochloride, and Tolcapone As Potential Therapeutics for Colorectal Cancers

Overview

Journal Front Bioinform

Specialty Biology

Date 2022 Oct 28

PMID 36303724

Authors

Hande Beklen

Sema Arslan

Gizem Gulfidan

Beste Turanli

Pemra Ozbek

Betul Karademir Yilmaz

Kazim Yalcin Arga

Affiliations

Soon will be listed here.

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 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 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.

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