Identification of candidate molecular targets of the novel antineoplastic antimitotic NP-10

Takuya Yokoyama, Masaki Yukuhiro, Yuka Iwasaki, Chika Tanaka, Kazunari Sankoda, Risa Fujiwara, Atsushi Shibuta, Taishi Higashi, Keiichi Motoyama, Hidetoshi Arima, Kazumasa Yoshida, Nozomi Sugimoto, Hiroyuki Morimoto, Hidetaka Kosako, Takashi Ohshima, Masatoshi Fujita

研究成果: Contribution to journalArticle査読

2 被引用数 (Scopus)

抄録

We previously reported the identification of a novel antimitotic agent with carbazole and benzohydrazide structures: N′-[(9-ethyl-9H-carbazol-3-yl)methylene]-2-iodobenzohydrazide (code number NP-10). However, the mechanism(s) underlying the cancer cell-selective inhibition of mitotic progression by NP-10 remains unclear. Here, we identified NP-10-interacting proteins by affinity purification from HeLa cell lysates using NP-10-immobilized beads followed by mass spectrometry. The results showed that several mitosis-associated factors specifically bind to active NP-10, but not to an inactive NP-10 derivative. Among them, NUP155 and importin β may be involved in NP-10-mediated mitotic arrest. Because NP-10 did not show antitumor activity in vivo in a previous study, we synthesized 19 NP-10 derivatives to identify more effective NP-10-related compounds. HMI83-2, an NP-10-related compound with a Cl moiety, inhibited HCT116 cell tumor formation in nude mice without significant loss of body weight, suggesting that HMI83-2 is a promising lead compound for the development of novel antimitotic agents.

本文言語英語
論文番号16825
ジャーナルScientific reports
9
1
DOI
出版ステータス出版済み - 12 1 2019

All Science Journal Classification (ASJC) codes

  • 一般

フィンガープリント

「Identification of candidate molecular targets of the novel antineoplastic antimitotic NP-10」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル