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PLoS One ; 7(9): e44889, 2012.
Article in English | MEDLINE | ID: mdl-23028663

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.


Subject(s)
Adenosine Triphosphatases/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , DNA-Binding Proteins/chemistry , Multiprotein Complexes/chemistry , Protein Subunits/metabolism , Thiazoles/metabolism , Thiazoles/pharmacology , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Chromosome Segregation/drug effects , Drug Resistance, Neoplasm/drug effects , Humans , Male , Mice , Mitosis/drug effects , Multiple Myeloma/pathology , Protein Binding , Risk , Xenograft Model Antitumor Assays
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