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Reversal gene expression assessment for drug repurposing, a case study of glioblastoma.
J Transl Med
January 2025
Informatics Core, Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, USA.
Background: Glioblastoma (GBM) is a rare brain cancer with an exceptionally high mortality rate, which illustrates the pressing demand for more effective therapeutic options. Despite considerable research efforts on GBM, its underlying biological mechanisms remain unclear. Furthermore, none of the United States Food and Drug Administration (FDA) approved drugs used for GBM deliver satisfactory survival improvement.
View Article and Find Full Text PDFAn Integrated Framework to Identify Prognostic Biomarkers and Novel Therapeutic Targets in Hepatocellular Carcinoma-Based Disabilities.
Biology (Basel)
November 2024
Artificial Intelligence and Cyber Futures Institute, Charles Sturt University, Bathurst, NSW 2795, Australia.
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors globally, significantly affecting liver functions, thus necessitating the identification of biomarkers and effective therapeutics to improve HCC-based disabilities. This study aimed to identify prognostic biomarkers, signaling cascades, and candidate drugs for the treatment of HCC through integrated bioinformatics approaches such as functional enrichment analysis, survival analysis, molecular docking, and simulation. Differential expression and functional enrichment analyses revealed 176 common differentially expressed genes from two microarray datasets, GSE29721 and GSE49515, significantly involved in HCC development and progression.
View Article and Find Full Text PDFMicrowave-Accelerated Synthesis of Novel Triphosphate Nucleoside Prodrugs: Expanding the Therapeutic Arsenal of Anticancer Agents.
Org Lett
January 2025
School of Chemistry, Cardiff University, Main Building, Park Place, CF10 3AT Cardiff, Wales, United Kingdom.
In this study, we report for the first time a microwave-accelerated synthesis of purine and pyrimidine nucleoside triphosphate prodrugs, whose γ phosphate is masked with an aryloxy moiety and an amino acid ester (γ-ProTriP). The synthetic utility of this method is illustrated by the synthesis of triphosphate prodrugs of clofarabine and gemcitabine, two FDA-approved anticancer drugs. These new prodrugs showed good chemical and rat serum stability.
View Article and Find Full Text PDFDeciphering the Therapeutic Potential of Novel Pentyloxyamide-Based Class I, IIb HDAC Inhibitors against Therapy-Resistant Leukemia.
J Med Chem
December 2024
Institute of Pharmaceutical und Medicinal Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
Histone deacetylase inhibitors (HDACi) are established anticancer drugs, especially in hematological cancers. This study aimed to design, synthesize, and evaluate a set of HDACi featuring a pentyloxyamide connecting unit linker region and substituted phenylthiazole cap groups. A structural optimization program yielded HDACi with nanomolar inhibitory activity against histone deacetylase class I/IIb enzymes.
View Article and Find Full Text PDFIdentification of Key Immune and Cell Cycle Modules and Prognostic Genes for Glioma Patients through Transcriptome Analysis.
Pharmaceuticals (Basel)
September 2024
Tianjin Tasly Digital Intelligence Chinese Medicine Development Co., Ltd., Tianjin 300410, China.
Article Synopsis
- Gliomas are highly aggressive brain tumors, and the study aimed to find prognostic markers related to their clinical traits by analyzing extensive datasets.
- Using WGCNA and LASSO regression, 11 key genes were identified, leading to the development of a prognostic risk score model that accurately predicts patient outcomes.
- The research highlights immune system interactions in glioma progression and suggests torin-1 and clofarabine as promising drugs that might effectively target these tumors.
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