RRC ID 44083
著者 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.
タイトル An anilinoquinazoline derivative inhibits tumor growth through interaction with hCAP-G2, a subunit of condensin II.
ジャーナル PLoS One
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.
巻・号 7(9)
ページ e44889
公開日 2012-1-1
DOI 10.1371/journal.pone.0044889
PII PONE-D-12-06136
PMID 23028663
PMC PMC3441599
MeSH Adenosine Triphosphatases / chemistry* Animals Antineoplastic Agents / metabolism* Antineoplastic Agents / pharmacology* Apoptosis / drug effects Cell Line, Tumor Cell Proliferation / drug effects Chromosome Segregation / drug effects DNA-Binding Proteins / chemistry* Drug Resistance, Neoplasm / drug effects Humans Male Mice Mitosis / drug effects Multiple Myeloma / pathology Multiprotein Complexes / chemistry* Protein Binding Protein Subunits / metabolism* Risk Thiazoles / metabolism* Thiazoles / pharmacology* Xenograft Model Antitumor Assays
IF 2.74
引用数 10
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 HeLa(RCB0007)