YPC-21661 and YPC-22026, novel small molecules, inhibit ZNF143 activity in vitro and in vivo

  • Cancer Sci. 2017 May;108(5):1042-1048. doi: 10.1111/cas.13199.
Hirotaka Haibara  1 ,  Ryuta Yamazaki  1 ,  Yukiko Nishiyama  1 ,  Masahiro Ono  1 ,  Tsuneyuki Kobayashi  1 ,  Atsuko Hokkyo-Itagaki  1 ,  Fukiko Nishisaka  1 ,  Hiroyuki Nishiyama  1 ,  Akinobu Kurita  1 ,  Takeshi Matsuzaki  1 ,  Hiroto Izumi  2 ,  Kimitoshi Kohno  2
Affiliations
  • 1. Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
  • 2. The University of Occupational and Environmental Health, Kitakyushu, Japan.
PMID: 28192620 DOI: 10.1111/cas.13199
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.

Keywords
ZNF143; anticancer drug; apoptosis; cell cycle; transcription factor.
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