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http://dx.doi.org/10.1016/j.drudis.2012.05.014 | DOI Listing |
Chem Res Toxicol
December 2024
Translational Pharmacokinetics, Pharmacodynamics and Investigative Toxicology, Janssen Research & Development, LLC, 2340 Beerse, Belgium.
The β-amyloid precursor protein-cleaving enzyme 1 (BACE1) inhibitor JNJ-54861911, a candidate for the treatment of Alzheimer's disease, was withdrawn from clinical trials due to drug-induced liver injury (DILI). This paper describes our investigation of the metabolism of JNJ-54861911 to understand the potential contribution to the observed DILI. In human hepatocytes, JNJ-54861911 is metabolized by CYP450 3A4 to a reactive intermediate (RI), which undergoes glutathione (GSH) addition at C6 of the 2-amino-4-methyl-1,3-thiazin-4-yl moiety via glutathione S-transferase α1 (GSTA1) catalysis.
View Article and Find Full Text PDFMethodsX
December 2024
School of Natural and Environmental Sciences, Newcastle University, Kings Road, Newcastle upon Tyne, England NE1 7RU, United Kingdom.
Clin Microbiol Rev
December 2024
Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.
SUMMARYThe opportunistic pathogen (Mab) causes fatal lung infections that bear similarities-and notable differences-with tuberculosis (TB) pulmonary disease. In contrast to TB, no antibiotic is formally approved to treat Mab disease, there is no reliable cure, and the discovery and development pipeline is incredibly thin. Here, we discuss the factors behind the unsatisfactory cure rates of Mab disease, namely intrinsic resistance and persistence of the pathogen, and the use of underperforming, often parenteral and toxic, repurposed drugs.
View Article and Find Full Text PDFEnterolactone, coumaric acid and vitexin are polyphenolic compounds present in a variety of fruits, vegetables, cereals and plants. These bioactive compounds are in high demand due to their antioxidant property in various tissues and organs. The purpose of this study was to develop a simultaneous extraction method, an aqueous two-phase extraction (ATPE) method, that would enable the extraction of these compounds from .
View Article and Find Full Text PDFClin Pract
July 2024
Department of Public Health, Medical University of Warsaw, 02-091 Warszawa, Poland.
Unlabelled: Clinical trials, by contributing to the development of diagnostics and to the search for modern, more effective, and safer therapies, have become one of the most important elements of the healthcare system. They enable the introduction of innovative drugs and treatments that can significantly improve patients' quality of life. Not only does this research help to understand disease mechanisms, but it also enables the personalization of therapy, which often increases the effectiveness of treatment.
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