A novel series of quinolinyl-methylene-thiazolinones has been identified as potent and selective cyclin-dependent kinase 1 (CDK1) inhibitors. Their synthesis and structure activity relationships (SAR) are described. Representative compounds from this class reversibly inhibit CDK1 activity in vitro, and block cell cycle progression in human tumor cell lines, suggesting a potential use as antitumor agents.
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http://dx.doi.org/10.1016/j.bmcl.2007.01.081 | DOI Listing |
Int J Biol Macromol
January 2025
Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, Ministry of Education, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, China; Department of Rehabilitation Medicine, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Cancer Hospital, Qingdao, Shandong 266000, China. Electronic address:
In contemporary times, the waning effectiveness of antibiotics against bacterial infections is progressively giving rise to significant concerns in public health. Although photodynamic technology possesses a potent ability to deactivate bacteria, its non-selective attack on normal cells poses potential side effects. Hence, in this study, a boric acid-substituted phthalocyanine photosensitizer (BAPc) was synthesized, exhibiting remarkable bacterial targeting capability.
View Article and Find Full Text PDFComput Biol Med
January 2025
School of Automation Science and Engineering, South China University of Technology, Guangzhou, China. Electronic address:
Breast cancer poses a significant health threat worldwide. Contrastive learning has emerged as an effective method to extract critical lesion features from mammograms, thereby offering a potent tool for breast cancer screening and analysis. A crucial aspect of contrastive learning is negative sampling, where the selection of hard negative samples is essential for driving representations to retain detailed lesion information.
View Article and Find Full Text PDFJ Med Chem
January 2025
Pharmaron Beijing Co., Ltd., 6 Taihe Road, BDA, Beijing 100176, P. R. China.
Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.
View Article and Find Full Text PDFMol Pharm
January 2025
Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina 27402, United States.
The fungal metabolite verticillin A is a potent and selective histone methyltransferase inhibitor. It regulates apoptosis, the cell cycle, and stress response, and displays potent activity in the suppression of tumor cell growth in several different in vivo models. Verticillin A sensitizes pancreatic cancer cells to anti-PD-1 immunotherapy by regulating PD-L1 expression.
View Article and Find Full Text PDFObesity-associated inflammation is characterized by macrophage infiltration into peripheral tissues, contributing to the progression of prediabetes and type 2 diabetes (T2D). The enzyme 12-lipoxygenase (12-LOX) catalyzes the formation of pro-inflammatory eicosanoids and is known to promote the migration of macrophages, yet its role in obesity-associated inflammation remains incompletely understood. Furthermore, differences between mouse and human orthologs of 12-LOX have limited efforts to study existing pharmacologic inhibitors of 12-LOX.
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