Repurposing of an Antifungal Drug against Gastrointestinal Stromal Tumors

Abstract

Drug discovery is an important research area to improve human health. Currently, treatment of gastrointestinal stromal tumors (GISTs) is unsuccessful due to drug-resistance, hence, there is a demand for alternatives. Often, there is limited time available for toxicological assessments and a lack of safer drugs. It is possible to identify new drugs from existing approved drugs possessing another purpose in the clinical lines. In this study, virtual screening of some Food and Drug Administration (FDA-USA) approved and available antifungal and antineoplastic drugs were performed against GISTs based on docking affinity of human platelet-derived growth factor receptor alpha (PDGFRA) with these drugs to identify a suitable PDGFRA inhibitor for saving the time required for toxicity screening. The protein and ligand-binding affinity were investigated for five FDA approved antineoplastic and thirty-six antifungal drugs against PDGFRA using the AutoDock (AD) and AutoDock Vina (ADV) software. Based on docking score and inhibition constant (Ki), Itraconazole was predicted as a better PDGFRA inhibitor among all the computationally tested drugs.

Current trends and future prospects of drug repositioning in gastrointestinal oncology

“…Levosimendan shows anti-cancer activity against various cancers by directly inhibiting RIOK1 and RNA processing enzymes ( Lim et al, 2019 ). Similarly, Arulanandam CD et al (2021) suggested itraconazole as a better inhibitor of platelet-derived growth factor receptor alpha (PDGFRA) compared to other antifungal drugs for treating gastrointestinal stromal tumors (GISTs) ( Arulanandam et al, 2021 ).…”