Reference - Detail
| RRC ID | 44083 |
|---|---|
| Author | 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. |
| Title | An anilinoquinazoline derivative inhibits tumor growth through interaction with hCAP-G2, a subunit of condensin II. |
| Journal | 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. |
| Volume | 7(9) |
| Pages | e44889 |
| Published | 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 |
| Times Cited | 10 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 8 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | HeLa(RCB0007) |