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© 2017. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Zinc‐finger protein 143 (ZNF143) is a transcription factor that is involved in anticancer drug resistance and cancer cell survival. In the present study, we identified a novel small molecule N‐(5‐bromo‐2‐methoxyphenyl)‐3‐(pyridine‐3‐yl) propiolamide (YPC‐21661) that inhibited ZNF143 promoter activity and down‐regulated the expression of the ZNF143‐regulated genes, RAD51, PLK1, and Survivin, by inhibiting the binding of ZNF143 to DNA. In addition, YPC‐21661 was cytotoxic and induced apoptosis in the human colon cancer cell line, HCT116 and human prostate cancer cell line, PC‐3. 2‐(pyridine‐3‐ylethynyl)‐5‐(2‐(trifluoromethoxy)phenyl)‐1,3,4‐oxadiazole (YPC‐22026), a metabolically stable derivative of YPC‐21661, induced tumor regression accompanied by the suppression of ZNF143‐regulated genes in a mouse xenograft model. The present study revealed that the inhibition of ZNF143 activity by small molecules induced tumor regression in vitro and in vivo; therefore, ZNF143 is a promising target of cancer therapeutics.

Details

Title
YPC‐21661 and YPC‐22026, novel small molecules, inhibit ZNF143 activity in vitro and in vivo
Author
Haibara, Hirotaka 1   VIAFID ORCID Logo  ; Yamazaki, Ryuta 1 ; Nishiyama, Yukiko 1 ; Ono, Masahiro 1 ; Kobayashi, Tsuneyuki 1 ; Atsuko Hokkyo‐Itagaki 1 ; Nishisaka, Fukiko 1 ; Nishiyama, Hiroyuki 1 ; Kurita, Akinobu 1 ; Matsuzaki, Takeshi 1 ; Izumi, Hiroto 2 ; Kohno, Kimitoshi 2 

 Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan 
 The University of Occupational and Environmental Health, Kitakyushu, Japan 
Pages
1042-1048
Section
ORIGINAL ARTICLES
Publication year
2017
Publication date
May 2017
Publisher
John Wiley & Sons, Inc.
ISSN
13479032
e-ISSN
13497006
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2289413437
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.