Open AccessYPC‐21661 and YPC‐22026, novel small molecules, inhibit ZNF143 activity in vitro and in vivo
Author(s) -
Haibara Hirotaka,
Yamazaki Ryuta,
Nishiyama Yukiko,
Ono Masahiro,
Kobayashi Tsuneyuki,
HokkyoItagaki Atsuko,
Nishisaka Fukiko,
Nishiyama Hiroyuki,
Kurita Akinobu,
Matsuzaki Takeshi,
Izumi Hiroto,
Kohno Kimitoshi
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13199
Subject(s) - small molecule , biology , in vivo , cancer cell , cancer , chemistry , cancer research , microbiology and biotechnology , biochemistry , genetics
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.