The development and synthesis of potent p38alpha MAP kinase inhibitors containing a 2H-quinolizin-2-one platform is described. Evolution of the 2H-quinolizin-2-one series from an early lead to solving off target activity and pharmacokinetic issues is also discussed.
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http://dx.doi.org/10.1016/j.bmcl.2010.03.069 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Department of Biochemistry, Brandeis University, Waltham, MA 02454.
Reversible protein phosphorylation directs essential cellular processes including cell division, cell growth, cell death, inflammation, and differentiation. Because protein phosphorylation drives diverse diseases, kinases and phosphatases have been targets for drug discovery, with some achieving remarkable clinical success. Most protein kinases are activated by phosphorylation of their activation loops, which shifts the conformational equilibrium of the kinase toward the active state.
View Article and Find Full Text PDFNutrients
November 2024
Department of Food Science and Technology, Korea National University of Transportation, Jeungpyeong 27909, Republic of Korea.
Background/objectives: Particulate matter (PM) is an environmental pollutant that negatively affects human health, particularly skin health. In this study, we investigated the inhibitory effects of broccoli sprout extract (BSE) on PM-induced skin aging and inflammation in human keratinocytes.
Methods: HaCaT keratinocytes were pretreated with BSE before exposure to PM.
Proc Natl Acad Sci U S A
December 2024
Joint National Laboratory for Antibody Drug Engineering, The First Affiliated Hospital, School of Medicine, Henan University, Kaifeng 475004, China.
Molecules
November 2024
Postgraduate Program in Natural Products and Bioactive Synthetics, Federal University of Paraíba, João Pessoa 58051-970, PB, Brazil.
Colorectal cancer remains a significant cause of mortality worldwide. A spiro-acridine derivative, ()-1'-((4-bromobenzylidene)amino)-5'-oxo-1',5'-dihydro-10-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-19), showed significant cytotoxicity in HCT-116 colorectal carcinoma cells (half maximal inhibitory concentration, IC50 = 10.35 ± 1.
View Article and Find Full Text PDFBMC Musculoskelet Disord
November 2024
Department of Orthopedics and Department of Sports Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107# Yanjiang West Road, Guangzhou, Guangdong Province, 510120, China.
Background: The global incidence of frozen shoulder (FS) (2% ~ 5%) and osteoporosis (OP) is high (9.1%-12.1%).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!