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Increasing brain half-life of antibodies by additional binding to myelin oligodendrocyte glycoprotein, a CNS specific protein.
Fluids Barriers CNS
January 2025
Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven - University of Leuven, O&N II Herestraat 49 box 820, 3000, Leuven, Belgium.
Background: Therapeutic antibodies for the treatment of neurological disease show great potential, but their applications are rather limited due to limited brain exposure. The most well-studied approach to enhance brain influx of protein therapeutics, is receptor-mediated transcytosis (RMT) by targeting nutrient receptors to shuttle protein therapeutics over the blood-brain barrier (BBB) along with their endogenous cargos. While higher brain exposure is achieved with RMT, the timeframe is short due to rather fast brain clearance.
View Article and Find Full Text PDFThe crosstalk between SND1 and PDCD4 is associated with chemoresistance of non-small cell lung carcinoma cells.
Cell Death Discov
January 2025
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is highly resistant to chemo- or radiation therapy, which poses a huge challenge for treatment of advanced NSCLC. Previously, we demonstrated the oncogenic role of Tudor Staphylococcal nuclease (TSN, also known as Staphylococcal nuclease domain-containing protein 1, SND1), in regulating chemoresistance in NSCLC cells.
View Article and Find Full Text PDFAntiproliferative activity of selenium-enriched coumarin derivatives on the SK-N-SH neuroblastoma cell line: Mechanistic insights.
Eur J Med Chem
January 2025
Lab of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Deqing, 313299, China; Institute of Drug Development & Chemical Biology, Zhejiang University of Technology, Deqing, 313299, China; Zhejiang Jieyuan Med-Tech Co., Ltd., Hangzhou, 311113, China. Electronic address:
Thirty selenium-containing coumarin derivatives were synthesized and evaluated for inhibitory activity against 17 malignant tumor cell lines. Among these, compound 11i demonstrated the most potent inhibition of neuroblastoma SK-N-SH cells, with an IC of 2.5 ± 0.
View Article and Find Full Text PDFNexinhib20 inhibits JFC1-mediated mobilization of a subset of CD11b/CD18+ vesicles decreasing integrin avidity, but does not inhibit Rac1.
J Leukoc Biol
January 2025
Department of Molecular and Cellular Biology, The Scripps Research Institute, La Jolla, CA.
Regulated sequential exocytosis of neutrophil granules is essential in orchestrating the innate immune response, while uncontrolled secretion causes inflammation. We developed and characterized Nexinhib20, a small-molecule inhibitor that targets azurophilic granule exocytosis in neutrophils by blocking the interaction between the small GTPase Rab27a and its effector JFC1. Its therapeutic potential has been demonstrated in several pre-clinical models of inflammatory disease.
View Article and Find Full Text PDFDiscovery of DCAF16 Binders for Targeted Protein Degradation.
ACS Chem Biol
January 2025
Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.
Conventional small-molecule drugs primarily operate by inhibiting protein function, but this approach is limited when proteins lack well-defined ligand-binding pockets. Targeted protein degradation (TPD) offers an alternative approach by harnessing cellular degradation pathways to eliminate specific proteins. Recent studies have expanded the potential of TPD by identifying additional E3 ligases, with DCAF16 emerging as a promising candidate for facilitating protein degradation through both proteolysis-targeting chimera (PROTAC) and molecular glue mechanisms.
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