作者
Richard A Burkhart, Yu Peng, Zoë A Norris, Renée M Tholey, Vanessa A Talbott, Qin Liang, Yongxing Ai, Kathy Miller, Shruti Lal, Joseph A Cozzitorto, Agnieska K Witkiewicz, Charles J Yeo, Matthew Gehrmann, Andrew Napper, Jordan M Winter, Janet A Sawicki, Zhihao Zhuang, Jonathan R Brody
发表日期
2013/8/1
期刊
Molecular Cancer Research
卷号
11
期号
8
页码范围
901-911
出版商
American Association for Cancer Research
简介
Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related death in the United States, with a 95% five-year mortality rate. For over a decade, gemcitabine (GEM) has been the established first-line treatment for this disease despite suboptimal response rates. The development of PARP inhibitors that target the DNA damage repair (DDR) system in PDA cells has generated encouraging results. Ubiquitin-specific peptidase 11 (USP11), an enzyme that interacts with the DDR protein BRCA2, was recently discovered to play a key role in DNA double-strand break repair and may be a novel therapeutic target. A systematic high-throughput approach was used to biochemically screen 2,000 U.S. Food and Drug Administration (FDA)-approved compounds for inhibition of USP11 enzymatic activity. Six pharmacologically active small molecules that inhibit USP11 enzymatic activity were …
学术搜索中的文章
RA Burkhart, Y Peng, ZA Norris, RM Tholey, VA Talbott… - Molecular Cancer Research, 2013