Gemcitabine is a nucleoside analog that has been used widely as an anticancer drug for the treatment of a variety of conditions, including ovarian, bladder, non-small-cell lung, pancreatic, and breast cancer. However, enzymatic deamination, fast systemic clearance, and the emergence of chemoresistance have limited its efficacy. Different prodrug strategies have been explored in recent years, seeking to obtain better pharmacokinetic properties, efficacy, and safety. Different drug delivery strategies have also been employed, seeking to transform gemcitabine into a targeted medicine. This review will provide an overview of the recent developments in gemcitabine prodrugs and their effectiveness in treating cancerous tumors.
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http://dx.doi.org/10.3390/genes13030466 | DOI Listing |
Cancer Sci
January 2025
Department of Drug Discovery and Biomedical Sciences, Faculty of Medicine, Saga University, Saga, Japan.
DNA methylation is an enzyme-driven epigenetic modification that must be precisely regulated to maintain cellular homeostasis. Aberrant methylation status, especially hypermethylation of the promoter sites of tumor-suppressor genes, is observed in human malignancies and is a proven target for cancer therapy. The first-generation DNA demethylating agents, azacitidine and decitabine, are widely used for treating several hematological malignancies.
View Article and Find Full Text PDFInt J Pharm
January 2025
Department of Pharmaceutics, College of Pharmacy, Chongqing Medical University, Chongqing 400016 China. Electronic address:
Loading drug-maleimide (MAL) conjugates into liposomes preloaded with glutathione (GSH) can prepare the liposome encapsulating GSH-conjugated prodrugs, which serve as a feasible way to construct liposomal formulation. However, the effects ofthelinker on the development of this liposomal system remained unclear. Herein, docetaxel (DTX)-MAL conjugates linked by various linkers were used for such studies.
View Article and Find Full Text PDFChemMedChem
January 2025
UMR-CNRS 7285, Institut de Chimie des Milieux et des Matériaux de Poitiers, groupe « Systèmes Moléculaires Programmés », Faculté des Sciences Fondamentales et Appliquées, 4 rue Michel Brunet, TSA 51106, 86073, Poitiers, FRANCE.
The development of novel therapeutic strategies enabling the selective destruction of tumors while sparing healthy tissues is of great interest to improve the efficacy of cancer chemotherapy. In this context, we designed a β-glucuronidase-responsive albumin-binding prodrug programmed to release a potent Isocombretastatin A-4 analog within the tumor microenvironment. When injected at a non-toxic dose in mice bearing orthotopic triple-negative mammary tumors, this prodrug produced a significant anticancer activity, therefore offering a valuable alternative to the systemic administration of the parent drug.
View Article and Find Full Text PDFClin Infect Dis
January 2025
Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
The recent US Food and Drug Administration approval of pivmecillinam-an oral prodrug of the amidinopenicillin antibiotic mecillinam-presents a valuable opportunity to address the need for new treatments for uncomplicated urinary tract infection (uUTI). We report findings of a systematic literature review of the safety profile of pivmecillinam/mecillinam based on more than 40 years' experience, mainly in Europe and Canada, to describe its tolerability profile and identify any important safety signals. In total, 110 eligible publications were identified describing use of pivmecillinam/mecillinam as monotherapy or in combination, for treatment of uUTI or other infectious conditions.
View Article and Find Full Text PDFDrug Deliv Transl Res
January 2025
Development and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Meteria Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China.
TXA9, a cardiac glycoside isolated from the root of Streptocaulon juventas (Lour.) Merr., with better therapeutic effect in vitro on non-small cell lung cancer (NSCLC) than cisplatin and has no toxic side effects on the body.
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