國家衛生研究院 NHRI:Item 3990099045/7936
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    题名: Generation and characterization of highly selective cathepsin S inhibitors with potentials against pancreatic cancer
    作者: Chang, WSW;Liao, CY;Chang, YH;Wu, TC;Wu, RJ;Chang, TN;Chang, JY;Lin, CC
    贡献者: National Institute of Cancer Research
    摘要: Cathepsin S (CTSS) is a critical cellular protease required for cancer development and metastasis. This proteolytic enzyme is often over-expressed by malignant tumor cells and secreted into the extracellular milieu to degrade surrounding matrix components. Here, we attempted to systematically generate and evaluate potential CTSS inhibitors in hope to identify potent candidates for use as antitumor agents. Detailed kinetic analysis revealed several lead compounds possess very low Ki values and high specificity against target CTSS protease. Results from ECM degradation assays demonstrated that these small molecules could protect fibronectin from CTSS-mediated degradation and consequently hinder tumor cell movement. Treating various pancreatic tumor cell lines with these CTSS inhibitors further resulted in a drastic decrease in cell migration and invasion. The test compounds also reduced the spread of pancreatic tumor cells in orthotopic animal model and thus prolonged mice survival. Finally, these lead molecules exhibited reasonable pharmacokinetic (PK) profiles, suggesting their potential as antitumor agents against pancreatic cancer.
    日期: 2013-04
    關聯: Cancer Research. 2013 Apr;73(8 Suppl. 1):Abstract number 5562.
    Link to: http://dx.doi.org/10.1158/1538-7445.am2013-5562
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000331220606041
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