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Importance of Sex-Dependent Differences for Dosing Selection and Optimization of Chemotherapeutic Drugs.
Chemotherapy
November 2024
Service and Laboratory of Clinical Pharmacology, Department of Internal Medicine and Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Background: Despite major advances in cancer treatment in the past years, there is a need to optimize chemotherapeutic drug dosing strategies to reduce toxicities, suboptimal responses, and the risk of relapse. Most cancer drugs have a narrow therapeutic index with substantial pharmacokinetics variability. Yet, current dosing approaches do not fully account for the complex pathophysiological characteristics of the patients.
View Article and Find Full Text PDFDNA-Thioguanine (DNA-TG) Is a Promising Novel Method to Predict Adverse Events to Thiopurine in Inflammatory Bowel Disease.
Inflamm Bowel Dis
October 2024
Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Personalization of thiopurine therapy: Current recommendations and future perspectives.
Acta Pharm
September 2024
University of Ljubljana, Faculty of Pharmacy, 1000 Ljubljana, Slovenia.
Article Synopsis
- Despite new treatments, small medicines like thiopurines (azathioprine, mercaptopurine, and thioguanine) are still really important for treating diseases like inflammatory bowel disease and cancer.
- The article talks about how doctors should customize dosages of thiopurines using genetic testing to make sure patients get the right amount based on their unique genes.
- It also mentions new research about genetics that could help doctors understand how people respond to thiopurines better in the future.
Identification of an RNA-binding perturbing characteristic for thiopurine drugs and their derivatives to disrupt CELF1-RNA interaction.
Nucleic Acids Res
October 2024
State Key Laboratory of Pharmaceutical Biotechnology, Drum Tower Hospital Affiliated to Medical School, School of Life Sciences, Nanjing University, Nanjing 210023, China.
RNA-binding proteins (RBPs) are attractive targets in human pathologies. Despite a number of efforts to target RBPs with small molecules, it is still difficult to develop RBP inhibitors, asking for a deeper understanding of how to chemically perturb RNA-binding activity. In this study, we found that the thiopurine drugs (6-mercaptopurine and 6-thioguanine) effectively disrupt CELF1-RNA interaction.
View Article and Find Full Text PDFNucleo(s)tide metabolism as basis for drug development; the Anne Simmonds award lecture.
Nucleosides Nucleotides Nucleic Acids
November 2024
Laboratory Medical Oncology, Amsterdam University Medical Centers, location VUMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Aberrant metabolism of purines and pyrimidines led to development of drugs for treatment of various diseases, such as inflammatory, neurological, cardiovascular, viral infections and cancer. Purine and Pyrimidine Symposia are characterized by close interactions, leading to extensive cross-fertilization on methodology and translating not only from bench-to-bedside, but also between various disciplines such as medicinal chemistry, pharmacology, oncology, virology, rheumatology, biochemistry, pediatrics, cardiology, surgery and immunology. This background was fundamental in our studies on how to optimize application of existing drugs (5-fluorouracil [5FU], thiopurines, antifolates such as methotrexate) but also to support development of novel drugs such as gemcitabine, novel antifolates, S-1, TAS-102 and fluorocyclopentenylcytosine.
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