@article{1ed0bd7793af48c595d4e18c177ce348,
title = "Discovery of novel mifepristone derivatives via suppressing KLF5 expression for the treatment of triple-negative breast cancer",
abstract = "Triple-negative breast cancer (TNBC) is one of the most malignant breast cancers currently with a lack of targeted therapeutic drugs. Accumulating evidence supports that KLF5 represents a novel therapeutic target for the treatment of basal TNBC. Our previous studies revealed that mifepristone is capable of suppressing TNBC cell proliferation and promoting cancer cell apoptosis by inhibiting KLF5 expression. Nevertheless, its anticancer efficacy is only modest with high dose. Moreover, its main metabolite N-desmethyl mifepristone with the removal of one methyl moiety results in a significant loss of antiproliferative activity, indicating an important pharmacophore domain around this methyl moiety. To improve the pharmacokinetic properties including metabolic stability and enhance the anticancer activities, a focused compound library by altering this sensitive metabolic region of mifepristone has been designed and synthesized for scaffold repurposing and structural optimization. Compound 17 (FZU-00,004) has been identified with an attractive anticancer profile against TNBC via suppressing KLF5 expression.",
keywords = "KLF5 expression, Mifepristone derivatives, Sensitive metabolic region, Triple-negative breast cancer",
author = "Yuqi Lin and Rong Liu and Ping Zhao and Jinxiang Ye and Zheng Zheng and Jingan Huang and Yingying Zhang and Yu Gao and Haiying Chen and Suling Liu and Jia Zhou and Ceshi Chen and Haijun Chen",
note = "Funding Information: This study was supported by grants from “Personalized Medicines – Molecular Signature-based Drug Discovery and Development”, a Strategic Priority Research Program of the Chinese Academy of Sciences (XDA12010303 to C. Chen), the National Nature Science Foundation of China (81325016 and U1602221 to C. Chen, 81322038, 81272930 and U1502222 to R. Liu, 81402781 to H. Chen), the Yunnan Applied Basic Research Key Projects (2015FA027 to R. Liu), the West Light Foundation of the Chinese Academy of Sciences (to R. Liu), the Youth Innovation Promotion Association and the Chinese Academy of Sciences (to R. Liu), Scientific Research Foundation for Returned Overseas Chinese Scholars (to H. Chen), grants P30 DA028821 and R01 DA038446 from the National Institutes of Health, Sanofi Innovation Awards (iAward) Program, Breast Cancer Research Program (BCRP) Breakthrough Award (BC160038) from the Department of Defense (DoD), and Cancer Prevention Research Institute of Texas (CPRIT) award (to J. Zhou). Funding Information: This study was supported by grants from “Personalized Medicines – Molecular Signature-based Drug Discovery and Development”, a Strategic Priority Research Program of the Chinese Academy of Sciences ( XDA12010303 to C. Chen), the National Nature Science Foundation of China ( 81325016 and U1602221 to C. Chen, 81322038 , 81272930 and U1502222 to R. Liu, 81402781 to H. Chen), the Yunnan Applied Basic Research Key Projects ( 2015FA027 to R. Liu), the West Light Foundation of the Chinese Academy of Sciences (to R. Liu), the Youth Innovation Promotion Association and the Chinese Academy of Sciences (to R. Liu), Scientific Research Foundation for Returned Overseas Chinese Scholars (to H. Chen), grants P30 DA028821 and R01 DA038446 from the National Institutes of Health , Sanofi Innovation Awards (iAward) Program, Breast Cancer Research Program (BCRP) Breakthrough Award ( BC160038 ) from the Department of Defense (DoD), and Cancer Prevention Research Institute of Texas (CPRIT) award (to J. Zhou). Publisher Copyright: {\textcopyright} 2018 Elsevier Masson SAS",
year = "2018",
month = feb,
day = "25",
doi = "10.1016/j.ejmech.2018.01.056",
language = "English (US)",
volume = "146",
pages = "354--367",
journal = "CHIM.THER.",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",
}