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ID 114952
Author
Yokoyama, Takuya Kyushu University
Yukuhiro, Masaki Kyushu University
Iwasaki, Yuka Kyushu University
Tanaka, Chika Kyushu University
Sankoda, Kazunari Kyushu University
Fujiwara, Risa Kyushu University
Shibuta, Atsushi Kyushu University
Higashi, Taishi Kumamoto University
Motoyama, Keiichi Kumamoto University
Arima, Hidetoshi Daiichi University of Pharmacy
Yoshida, Kazumasa Kyushu University
Sugimoto, Nozomi Kyushu University
Morimoto, Hiroyuki Kyushu University
Ohshima, Takashi Kyushu University
Fujita, Masatoshi Kyushu University
Content Type
Journal Article
Description
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.
Journal Title
Scientific Reports
ISSN
20452322
Publisher
Springer Nature
Volume
9
Start Page
16825
Published Date
2019-11-14
Rights
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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language
eng
TextVersion
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departments
Institute of Advanced Medical Sciences