Apoptosis signal-regulating kinase 1 (ASK1/MAP3K) is a mitogen-activated protein kinase family member shown to contribute to acute ischemia/reperfusion injury. Using structure-based drug design, deconstruction, and reoptimization of a known ASK1 inhibitor, a lead compound was identified. This compound displayed robust MAP3K pathway inhibition and reduction of infarct size in an isolated perfused heart model of cardiac injury.
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http://dx.doi.org/10.1021/acsmedchemlett.6b00481 | DOI Listing |
Expert Opin Ther Pat
December 2024
Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, China.
Introduction: Xanthine oxidase (XO) catalyzes the oxidation of both hypoxanthine and xanthine in the last two steps of the purine metabolic pathway, serving as a rate-limiting enzyme for uric acid production as well as a key target for the treatment of gout and other hyperuricemia-related conditions.
Areas Covered: This paper reviews XO inhibitors in patents from 2021 to the present. We summarize in detail the structural classes and characteristics, in vitro and in vivo biological results, and structure‒activity relationships of synthetic inhibitors, as well as the sources, specific structures, research methods, and biological activities of XO inhibitors from natural products.
Trop Med Infect Dis
November 2024
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
Tuberculosis (TB) is a global health challenge associated with considerable levels of illness and mortality worldwide. The development of innovative therapeutic strategies is crucial to combat the rise of drug-resistant TB strains. DNA Gyrase A (GyrA) and serine/threonine protein kinase (PknB) are promising targets for new TB medications.
View Article and Find Full Text PDFMetabolites
December 2024
Pharmacognosy and Pharmaceutical Chemistry Department, Faculty of Pharmacy, Taibah University, Al Madinah Al Munawarah 30001, Saudi Arabia.
is a highly multidrug-resistant pathogen resistant to almost all classes of antibiotics; new therapeutic strategies against this infectious agent are urgently needed. Shikimate kinase is an enzyme belonging to the shikimate pathway and has become a potential target for drug development. This work describes the search for Food and Drug Administration (FDA)-approved drugs and natural compounds, including gallic acid, that could be repurposed as selective shikimate kinase inhibitors by integrated computational and experimental approaches.
View Article and Find Full Text PDFJ Imaging
December 2024
College of Big Data and Intelligent Engineering, Southwest Forestry University, Kunming 650224, China.
Walnuts possess significant nutritional and economic value. Fast and accurate sorting of shells and kernels will enhance the efficiency of automated production. Therefore, we propose a FastQAFPN-YOLOv8s object detection network to achieve rapid and precise detection of unsorted materials.
View Article and Find Full Text PDFJ Med Chem
December 2024
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China.
Lipid metabolism disorder is the cause of one of the most significant metabolic changes in tumors. In the process of tumor occurrence and development, tumor cells choose a continuous metabolic adaptation to accommodate the changing environment to the maximum extent possible. In a variety of tumors, the uptake, production, and storage of lipids are generally upregulated.
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