1.A novel molecular targeting compound as K-samII/FGF-R2 phosphorylation inhibitor, Ki23057, for Scirrhous gastric cancer.
Nakamura K1, Yashiro M, Matsuoka T, Tendo M, Shimizu T, Miwa A, Hirakawa K. Gastroenterology. 2006 Nov;131(5):1530-41. Epub 2006 Aug 22.
BACKGROUND & AIMS: Scirrhous gastric carcinoma carries the highest mortality of all gastric cancers. The poor prognosis is reported to be associated with K-samII amplification, which encodes fibroblast growth factor receptor type 2 (FGF-R2). Ki23057, a newly developed small molecule-acting K-samII/FGF-R2 autophosphorylation inhibitor, is a tyrosine kinase inhibitor that competes with adenosine triphosphate for the binding site. The aim of the current study is to clarify the possibility of molecular target therapy with Ki23057 for treating scirrhous gastric cancer.
2.A FGFR2 inhibitor, Ki23057, enhances the chemosensitivity of drug-resistant gastric cancer cells.
Qiu H1, Yashiro M, Zhang X, Miwa A, Hirakawa K. Cancer Lett. 2011 Aug 1;307(1):47-52. doi: 10.1016/j.canlet.2011.03.015. Epub 2011 Apr 8.
AIM: The aim of this study was to clarify the ability of a FGFR2 inhibitor, Ki23057, to enhance the chemosensitivity of drug-resistant gastric cancer cell lines when used in combination with chemotherapeutic drugs.
3.A novel angiogenesis inhibitor, Ki23057, is useful for preventing the progression of colon cancer and the spreading of cancer cells to the liver.
Sakurai K1, Yamada N, Yashiro M, Matsuzaki T, Komatsu M, Ohira M, Miwa A, Hirakawa K. Eur J Cancer. 2007 Nov;43(17):2612-20. Epub 2007 Oct 18.
Ki23057 is a new, small synthetic tyrosine kinase inhibitor that blocks autophosphorylation of the VEGF receptor2 (VEGFR2). To determine the effect of Ki23057 as an anti-angiogenic agent, we studied the effect of Ki23057 for colon cancer and vascular endothelial cells in vitro and in vivo. Ki23057 inhibited VEGF-induced proliferation of human umbilical vein endothelial cells (HUVECs), whereas no inhibitory effect of Ki23057 on the proliferation of three colon cancer cells (LM-H3, LoVo and LS174T) was observed by means of the cell count assay. Ki23057 inhibited tube formation of HUVECs. Immunoprecipitation demonstrated that Ki23057 inhibited tyrosine phosphorylation of VEGFR2 in HUVECs. Ki23057 exhibited a significant inhibitory effect on the growth of the xenografted LM-H3 tumours and the spreading of cancer cells to the liver. Anti-CD31 antibody stained significantly fewer microvessels in the xenografted tumours treated with Ki23057 compared with controls.