CVS-3983, a selective matriptase inhibitor, suppresses the growth of androgen independent prostate tumor xenografts

The Prostate
Anna V GalkinDavid B Agus

Abstract

Matriptase, a type-II transmembrane serine protease, is expressed by cancers of epithelial origin including breast, colon, and prostate carcinomas and has been implicated in tumor growth and progression. We studied the effects of CVS-3983, a selective small molecule matriptase inhibitor, on the growth of the androgen independent (AI) CWR22R and CWRSA6 human prostate cancer xenograft models. CVS-3983 was administered i.p. twice-daily 7-days per week for 2-3 weeks to mice with established tumors. Measurements of tumor volume were made twice weekly. The effect of CVS-3983 on CWR22RV1 cell invasion through a reconstituted basement membrane matrix of proteins was also evaluated. Matriptase expression across the tumor lines was assessed by RT-PCR and Western blotting. CVS-3983 inhibited final mean tumor volume by 65.5% (n = 10, P = 0.0002) in the CWR22R model and by 56.2% (n = 8, P = 0.0017) in the CWRSA6 tumor model compared with vehicle-treated tumors. CVS-3983 did not inhibit the proliferation of CWR22RV1 cells in vitro; however, the small molecule did significantly reduce by 30.2% the invasion of these cells in vitro through a reconstituted basement membrane matrix. Molecular analysis of the xenograft tumors demonstrated high exp...Continue Reading

References

Jun 1, 1996·Seminars in Cancer Biology·W G Stetler-StevensonM Corcoran
Jul 3, 1997·International Journal of Cancer. Journal International Du Cancer·P A AndreasenM J Duffy
Aug 1, 1997·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M F PressK J Flom
Dec 23, 2000·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·H TanimotoT J O'Brien
Aug 24, 2001·Nature·S M DhanasekaranA M Chinnaiyan
Sep 28, 2001·Biochemical and Biophysical Research Communications·S SatomiT Fushiki
Oct 2, 2001·CA: a Cancer Journal for Clinicians·R T GreenleeM Thun
Nov 7, 2001·The Journal of Biological Chemistry·Rainer FriedrichEdwin L Madison
Jul 19, 2002·Journal of Cellular Physiology·Serenella M PupaElda Tagliabue

❮ Previous
Next ❯

Citations

Jun 16, 2005·Current Opinion in Pharmacology·Paul Elvin, Andrew P Garner
Oct 5, 2011·Journal of Medicinal Chemistry·Zhenghong XuChen-Yong Lin
Feb 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Marguerite S BuzzaToni M Antalis
Aug 30, 2008·American Journal of Respiratory Cell and Molecular Biology·Sabina JanciauskieneSadis Matalon
Apr 20, 2012·PloS One·Arkadiusz WelmanMargaret C Frame
Jul 14, 2006·Molecular Medicine·Karin ListRoman Szabo
Feb 27, 2009·Future Oncology·Karin List
Nov 20, 2013·Virchows Archiv : an International Journal of Pathology·Sang Yun HaSeok-Hyung Kim
Mar 29, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ami S BhattCharles S Craik
Oct 1, 2014·Cancers·Makiko Kawaguchi, Hiroaki Kataoka
Mar 29, 2006·FEBS Letters·Antoine DésiletsRichard Leduc
Apr 20, 2010·Biochemical and Biophysical Research Communications·Hyo Seon LeeDongeun Park
Nov 12, 2014·Journal of Medicinal Chemistry·Dominic DuchêneRafael Najmanovich
Nov 28, 2008·Bioorganic & Medicinal Chemistry Letters·Torsten SteinmetzerAndrea Schweinitz
Oct 31, 2009·Journal of Cellular and Molecular Medicine·Lluis-A Lopez-Barcons
May 29, 2010·The Biochemical Journal·Toni M AntalisSarah Netzel-Arnett
Jun 30, 2015·Journal of Enzyme Inhibition and Medicinal Chemistry·Erzsebet Pászti-GereTorsten Steinmetzer
Jan 4, 2015·Bioorganic & Medicinal Chemistry Letters·Rajeev GoswamiMurali Ramachandra
May 12, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Alexander MaiwaldTorsten Steinmetzer
Apr 15, 2016·Biological Chemistry·Andrew S MurrayKarin List
Apr 1, 2005·American Journal of Physiology. Cell Physiology·Michael D OberstChen-Yong Lin
Apr 5, 2019·Future Medicinal Chemistry·Vishnu C Damalanka, James W Janetka
Mar 9, 2007·American Journal of Physiology. Cell Physiology·Ming-Shyue LeeChen-Yong Lin
Jul 15, 2015·American Journal of Physiology. Cell Physiology·Abdo J NajyHyeong-Reh C Kim
Sep 19, 2019·Cancer Metastasis Reviews·Carly E Martin, Karin List
Oct 20, 2018·Current Medicinal Chemistry·Peng Xu, Mingdong Huang
Nov 22, 2016·The FEBS Journal·Lauren M Tanabe, Karin List

❮ Previous
Next ❯

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