An anilinoquinazoline derivative inhibits tumor growth through interaction with hCAP-G2, a subunit of condensin II.

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.
Authors	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
Journal	PloS one (PLoS One) Vol. 7 Issue 9 Pg. e44889 ( 2012) ISSN: 1932-6203 [Electronic] United States
PMID	23028663 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents DNA-Binding Proteins Multiprotein Complexes Protein Subunits Thiazoles condensin complexes 2-anilino-5-thiazolinone Adenosine Triphosphatases
Topics	Adenosine Triphosphatases (chemistry) Animals Antineoplastic Agents (metabolism, 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, pharmacology) Xenograft Model Antitumor Assays

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