title: YPC-21661 and YPC-22026, novel small molecules, inhibit ZNF143 activity in vitro and in vivo.
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.
authors.affiliation: Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
authors.forename: Hirotaka
authors.identifier: http://orcid.org/0000-0001-5492-0134
authors.initials: H
authors.lastname: Haibara
authors.affiliation: Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Yamazaki
authors.affiliation: Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nishiyama
authors.affiliation: Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.affiliation: Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
authors.forename: Tsuneyuki
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hokkyo-Itagaki
authors.affiliation: Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
authors.forename: Fukiko
authors.initials: F
authors.lastname: Nishisaka
authors.affiliation: Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishiyama
authors.affiliation: Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Kurita
authors.affiliation: Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsuzaki
authors.affiliation: The University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.affiliation: The University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kohno
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000494:pharmacology*; D015534:Trans-Activators / Q000037:antagonists & inhibitors*; D014157:Transcription Factors / Q000037:antagonists & inhibitors
chemical_list: D054852:Small Molecule Libraries; D015534:Trans-Activators; D014157:Transcription Factors; C114253:ZNF143 protein, human
keywords: ZNF143; anticancer drug; apoptosis; cell cycle; transcription factor