國家衛生研究院 NHRI:Item 3990099045/7936

NHRI > National Institute of Cancer Research > Jang-Yang Chang > Conference Papers/Meeting Abstract > Item 3990099045/7936

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/7936

Title:	Generation and characterization of highly selective cathepsin S inhibitors with potentials against pancreatic cancer
Authors:	Chang, WSW;Liao, CY;Chang, YH;Wu, TC;Wu, RJ;Chang, TN;Chang, JY;Lin, CC
Contributors:	National Institute of Cancer Research
Abstract:	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.
Date:	2013-04
Relation:	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
Appears in Collections:	[Jang-Yang Chang] Conference Papers/Meeting Abstract [Wun-Shaing Wayne Chang] Conference Papers/Meeting Abstract

Files in This Item:

File	Description	Size	Format
ISI000331220606041.pdf		24Kb	Adobe PDF	581	View/Open

Loading...