A new sub-class of p38 inhibitors represented by 7-amino-naphthyridone have been discovered. Benchmark compound 16 potently inhibited p38 in vitro, was functionally active, and displayed excellent pharmacokinetic profiles in two animal species. Compound 16 reduced inflammation in animal disease models at EC(50) doses as low as 0.2mpk.
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http://dx.doi.org/10.1016/j.bmcl.2006.06.084 | DOI Listing |
Biochemistry (Mosc)
December 2024
Moscow Institute of Physics and Technology, Dolgoprudny, 141701, Russia.
Activation of the p38 mitogen-activated protein kinase (MAPK) pathways is vital in regulating cell growth, differentiation, apoptosis, and stress response, significantly affecting tumorigenesis and cancer progression. We developed a bioinformatic technique to construct an interactome network-based molecular pathways for genes of interest and quantify their activation levels using high-throughput gene expression data. This study is focused on the p38α, p38β, p38γ, and p38δ kinases, examining their activation levels (PALs) based on transcriptomic data and their associations with survival and drug responsiveness across various cancer types.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
College of Pharmacy, QU Health, Qatar University, Doha 2713, Qatar.
Human epidermal growth factor receptor 2 (HER2) is a subtype of breast cancer that is associated with poor prognosis and low survival rates. The discovery of novel anti-cancer agents to manage this subtype of cancer is still needed. ( is a plant species that is native to Qatar.
View Article and Find Full Text PDFBiomolecules
January 2025
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths globally, with a persistently low five-year survival rate of only 14-17%. High rates of metastasis contribute significantly to the poor prognosis of NSCLC, in which inflammation plays an important role by enhancing tumor growth, angiogenesis, and metastasis. Targeting inflammatory pathways within cancer cells may thus represent a promising strategy for inhibiting NSCLC metastasis.
View Article and Find Full Text PDFAnn Clin Lab Sci
November 2024
Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
Objective: The aim of the present study was to determine the effects of selenium-methylselenocysteine (MSC) on the viability, migration, and glycolysis of human ATC cell lines 8305 and BHT101 .
Methods: Cells were treated with MSC and viability was determined using the Cell Counting Kit 8 assay. The migratory ability of cells was detected using a Transwell migration assay, and the expression levels of proteins involved in the ERK1/2, JNK, and p38 signaling pathways were measured by western blotting.
FASEB J
January 2025
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Liver ischemia-reperfusion (IR) injury is a common complication following liver surgery, significantly impacting the prognosis of liver transplantation and other liver surgeries. Betaine-homocysteine methyltransferase (BHMT), a crucial enzyme in the methionine cycle, has been previously confirmed the pivotal role in hepatocellular carcinoma, and it has also been demonstrated that BHMT inhibits inflammation, apoptosis, but its role in liver IR injury remains unknow. Following I/R injury, we found that BHMT expression was significantly upregulated in human liver transplant specimens, mice and hepatocytes.
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