論文

査読有り 国際誌
2019年12月

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

Scientific Reports
  • Hiroyuki Morimoto

9
1
開始ページ
16825
終了ページ
16825
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41598-019-53259-2

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.

Web of Science ® 被引用回数 : 1

リンク情報
DOI
https://doi.org/10.1038/s41598-019-53259-2
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31727981
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856148
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000496416000035&DestApp=WOS_CPL
URL
http://www.scopus.com/inward/record.url?eid=2-s2.0-85075058421&partnerID=MN8TOARS
ID情報
  • DOI : 10.1038/s41598-019-53259-2
  • ISSN : 2045-2322
  • ORCIDのPut Code : 66167164
  • PubMed ID : 31727981
  • PubMed Central 記事ID : PMC6856148
  • SCOPUS ID : 85075058421
  • Web of Science ID : WOS:000496416000035

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