TY - JOUR
T1 - An Anilinoquinazoline Derivative Inhibits Tumor Growth through Interaction with hCAP-G2, a Subunit of Condensin II
AU - Shiheido, Hirokazu
AU - Naito, Yuhei
AU - Kimura, Hironobu
AU - Genma, Hiroaki
AU - Takashima, Hideaki
AU - Tokunaga, Mayuko
AU - Ono, Takao
AU - Hirano, Tatsuya
AU - Du, Wenlin
AU - Yamada, Taketo
AU - Doi, Nobuhide
AU - Iijima, Shiro
AU - Hattori, Yutaka
AU - Yanagawa, Hiroshi
PY - 2012/9/13
Y1 - 2012/9/13
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0044889
DO - 10.1371/journal.pone.0044889
M3 - Article
C2 - 23028663
AN - SCOPUS:84866403628
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 9
M1 - e44889
ER -
