Identification and pre-clinical testing of a reversible cathepsin protease inhibitor reveals anti-tumor efficacy in a pancreatic cancer model Journal Article
| Authors: | Elie, B. T.; Gocheva, V.; Shree, T.; Dalrymple, S. A.; Holsinger, L. J.; Joyce, J. A. |
| Article Title: | Identification and pre-clinical testing of a reversible cathepsin protease inhibitor reveals anti-tumor efficacy in a pancreatic cancer model |
| Abstract: | Proteolytic activity is required for several key processes in cancer development and progression, including tumor growth, invasion and metastasis. Accordingly, high levels of protease expression and activity have been found to correlate with malignant progression and poor patient prognosis in a wide variety of human cancers. Members of the papain family of cysteine cathepsins are among the protease classes that have been functionally implicated in cancer. Therefore, the discovery of effective cathepsin inhibitors has considerable potential for anti-cancer therapy. In this study we describe the identification of a novel, reversible cathepsin inhibitor, VBY-825, which has high potency against cathepsins B, L, S and V. VBY-825 was tested in a pre-clinical model of pancreatic islet cancer and found to significantly decrease tumor burden and tumor number. Thus, the identification of VBY-825 as a new and effective anti-tumor drug encourages the therapeutic application of cathepsin inhibitors in cancer. © 2010 Elsevier Masson SAS. |
| Keywords: | controlled study; unclassified drug; human cell; drug efficacy; nonhuman; antineoplastic agents; pancreatic neoplasms; antineoplastic agent; cell proliferation; animal cell; mouse; animals; mice; animal tissue; apoptosis; protease inhibitors; tumor volume; animal experiment; animal model; antineoplastic activity; drug potency; tumor regression; drug screening; drug evaluation, preclinical; drug design; structure activity relation; neovascularization, pathologic; cancer model; cancer invasion; tumor burden; neoplasm invasiveness; cathepsin b; cysteine proteinase inhibitor; cathepsins; disease models, animal; leucine; tumor vascularization; therapy; biological availability; sulfones; pancreas islet cell carcinoma; hydrocarbons, fluorinated; protease; cysteine cathepsin; cathepsin l; cathepsin s; cathepsin v; vby 825; drug identification |
| Journal Title: | Biochimie |
| Volume: | 92 |
| Issue: | 11 |
| ISSN: | 0300-9084 |
| Publisher: | Editions Scientifiques Elsevier |
| Date Published: | 2010-11-01 |
| Start Page: | 1618 |
| End Page: | 1624 |
| Language: | English |
| DOI: | 10.1016/j.biochi.2010.04.023 |
| PUBMED: | 20447439 |
| PROVIDER: | scopus |
| PMCID: | PMC3814225 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: BICMB" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work