Drug discovery has customarily focused on a de novo design approach, which is extremely expensive and takes several years to evolve before reaching the market. Discovering novel therapeutic benefits for the current drugs could contribute to new treatment alternatives for individuals with complex medical demands that are safe, inexpensive, and timely. In this consequence, when pharmaceutically yield and oncology drug efficacy appear to have hit a stalemate, drug repurposing is a fascinating method for improving cancer treatment. This review gathered about how in silico drug repurposing offers the opportunity to quickly increase the anticancer drug arsenal and, more importantly, overcome some of the limits of existing cancer therapies against both old and new therapeutic targets in oncology. The ancient nononcology compounds' innovative potential targets and important signaling pathways in cancer therapy are also discussed. This review also includes many plant-derived chemical compounds that have shown potential anticancer properties in recent years. Here, we have also tried to bring the spotlight on the new mechanisms to support clinical research, which may become increasingly essential in the future; at the same time, the unsolved or failed clinical trial study should be reinvestigated further based on the techniques and information provided. These encouraging findings, combined together, will through new insight on repurposing more non-oncology drugs for the treatment of cancer.
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http://dx.doi.org/10.4103/ijp.ijp_626_22 | DOI Listing |
In Silico Pharmacol
December 2024
Department of Bioinformatics, Alagappa University, Karaikudi, 630003 Tamil Nadu India.
Unlabelled: Drug repurposing is necessary to accelerate drug discovery and meet the drug needs. This study investigated the possibility of using fluvoxamine to inhibit the cellular metabolizing enzyme NUDT5 in breast cancer. Computational and experimental techniques were used to evaluate the structural flexibility, binding stability, and chemical reactivity of the drugs.
View Article and Find Full Text PDFEur J Pharmacol
December 2024
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei 10507, Taiwan; Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. Electronic address:
Multidrug resistance (MDR) remains a significant obstacle in cancer treatment, primarily attributable to the overexpression of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCG2 within cancer cells. These transporters actively diminish the effectiveness of cytotoxic drugs by facilitating ATP hydrolysis-dependent drug efflux, thereby reducing intracellular drug accumulation. Given the absence of approved treatments for multidrug-resistant cancers and the established benefits of combining tyrosine kinase inhibitors (TKIs) with conventional anticancer drugs, we investigate the potential of vodobatinib, a potent c-Abl TKI presently in clinical trials, to restore sensitivity to chemotherapeutic agents in multidrug-resistant cancer cells overexpressing ABCB1 and ABCG2.
View Article and Find Full Text PDFArch Microbiol
December 2024
Infectious Diseases Division, CSIR- Indian Institute of Integrative Medicine, Jammu, 180001, India.
Klebsiella pneumoniae is a leading cause of anti-microbial resistance in healthcare-associated infections that have posed a severe threat to neonatal and wider community. The escalating crises of antibiotic resistance have compelled researchers to explore an innovative arsenal beginning from natural resources to chemical modifications in order to overcome the ever-increasing resistance issues. The present review highlights the drug discovery efforts with a special focus on cutting-edge strategies in the hunt for potential drug candidates against MDR/XDR Klebsiella pneumoniae.
View Article and Find Full Text PDFProtein Sci
January 2025
Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
This study focuses on spastic paraplegia type 50 (SPG50), an adapter protein complex 4 deficiency syndrome caused by mutations in the adapter protein complex 4 subunit mu-1 (AP4M1) gene, and on the downstream alterations of the AP4M1 protein. We applied a battery of heterogeneous computational resources, encompassing two in-house tools described here for the first time, to (a) assess the druggability potential of AP4M1, (b) characterize SPG50-associated mutations and their 3D scenario, (c) identify mutation-tailored drug candidates for SPG50, and (d) elucidate their mechanisms of action by means of structural considerations on homology models of the adapter protein complex 4 core. Altogether, the collected results indicate R367Q as the mutation with the most promising potential of being corrected by small-molecule drugs, and the flavonoid rutin as best candidate for this purpose.
View Article and Find Full Text PDFNeurourol Urodyn
December 2024
Faculty of Medicine, Department of Urology, Hacettepe University, Ankara, Türkiye.
Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating pain condition of unknown etiology. Effective therapies for this condition could not have been developed in the last century. Drug repurposing is a practical strategy for enhancing patient access to successful therapies.
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