An Anilinoquinazoline Derivative Inhibits Tumor Growth through Interaction with hCAP-G2, a Subunit of Condensin II

Hirokazu Shiheido, Yuhei Naito, Hironobu Kimura, Hiroaki Genma, Hideaki Takashima, Mayuko Tokunaga, Takao Ono, Tatsuya Hirano, Wenlin Du, Taketo Yamada, Nobuhide Doi, Shiro Iijima, Yutaka Hattori, Hiroshi Yanagawa

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Abstract

We screened 46 novel anilinoquinazoline derivatives for activity to inhibit proliferation of a panel of human cancer cell lines. Among them, Q15 showed potent in vitro growth-inhibitory activity towards cancer cell lines derived from colorectal cancer, lung cancer and multiple myeloma. It also showed antitumor activity towards multiple myeloma KMS34 tumor xenografts in lcr/scid mice in vivo. Unlike the known anilinoquinazoline derivative gefitinib, Q15 did not inhibit cytokine-mediated intracellular tyrosine phosphorylation. Using our mRNA display technology, we identified hCAP-G2, a subunit of condensin II complex, which is regarded as a key player in mitotic chromosome condensation, as a Q15 binding partner. Immunofluorescence study indicated that Q15 compromises normal segregation of chromosomes, and therefore might induce apoptosis. Thus, our results indicate that hCAP-G2 is a novel therapeutic target for development of drugs active against currently intractable neoplasms.

Original languageEnglish
Article numbere44889
JournalPLoS One
Volume7
Issue number9
DOIs
Publication statusPublished - 2012 Sep 13

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Shiheido, H., Naito, Y., Kimura, H., Genma, H., Takashima, H., Tokunaga, M., Ono, T., Hirano, T., Du, W., Yamada, T., Doi, N., Iijima, S., Hattori, Y., & Yanagawa, H. (2012). An Anilinoquinazoline Derivative Inhibits Tumor Growth through Interaction with hCAP-G2, a Subunit of Condensin II. PLoS One, 7(9), [e44889]. https://doi.org/10.1371/journal.pone.0044889