LYG-202, a Newly Synthesized Flavonoid, Exhibits Potent Anti-angiogenic Activity In Vitro and In Vivo

10.1016/S0163-7258(02)00298-X 10.1002/med.10033 1994, 366, 351, 10.1007/978-1-4615-1833-4_25 4 Mojzis J, Varinska L, Mojzisova G, Kostova I, Mirossay L. Antiangiogenic effects of flavonoids and chalcones. Pharmacol Res. 2008;57:259–265. 5 Risau W. Mechanisms of angiogenesis. Nature. 1997;386: 671–674. 10.1038/nature04478 10.1158/0008-5472.CAN-04-2427 10.1016/j.jnutbio.2004.09.004 9 Joussen AM, Rohrschneider K, Reichling J, Kirchhof B, Kruse FE. Treatment of corneal neovascularization with dietary isoflavonoids and flavonoids. Exp Eye Res. 2000;71:483–487. 10 Dulak J. Nutraceuticals as anti-angiogenic agents: hopes and reality. J Physiol Pharmacol. 2005;56 Suppl 1:51–67. 11 Kandaswami C, Lee LT, Lee PP, Hwang JJ, Ke FC, Huang YT, et al. The antitumor activities of flavonoids. In Vivo. 2005;19:895–909. 10.1002/ptr.2283 10.1172/JCI107470 10.1006/bbrc.1999.1586 10.1074/jbc.274.50.35562 10.1016/j.bbrc.2007.06.155 17 Lu N, Yang Y, You QD, Ling Y, Gao Y, Gu HY, et al. Gambogic acid inhibits angiogenesis through suppressing vascular endothelial growth factor-induced tyrosine phosphorylation of KDR/Flk-1. Cancer Lett. 2007;258:80–89. 10.1016/j.lfs.2008.02.013 10.1038/380435a0 10.1006/excr.1994.1042 21 Hanahan D, Christofori G, Naik P, Arbeit J. Transgenic mouse models of tumour angiogenesis: the angiogenic switch, its molecular controls, and prospects for preclinical therapeutic models. Eur J Cancer. 1996;32A:2386–2393. 10.1023/A:1006493130855 10.1210/er.18.1.4 24 Cross MJ, Claesson-Welsh L. FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci. 2001;22:201–207. 10.1046/j.1538-7836.2003.00263.x VEIKKOLA T, 2000, 60, 203 27 Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999;13:9–22. 10.1016/S0008-6363(00)00268-6 10.1074/jbc.275.14.10661 10.1074/jbc.273.46.30336 31 Somanath PR, Malinin NL, Byzova TV. Cooperation between integrin alpha(nu)beta (3) and VEGFR2 in angiogenesis. Angiogenesis. 2009;12:177–185. 10.1074/jbc.273.47.31273 33 Cunningham BD, Threadgill MD, Groundwater PW, Dale IL, Hickman JA. Synthesis and biological evaluation of a series of flavones designed as inhibitors of protein tyrosine kinases. Anticancer Drug Des. 1992;7:365–384. 10.1016/S0014-5793(02)03630-X 35 Huang D, Ding Y, Luo WM, Bender S, Qian CN, Kort E, et al. Inhibition of MAPK kinase signaling pathways suppressed renal cell carcinoma growth and angiogenesis in vivo. Cancer Res. 2008;68:81–88. 36 Issbrucker K, Marti HH, Hippenstiel S, Springmann G, Voswinckel R, Gaumann A, et al. p38 MAP kinase – a molecular switch between VEGF-induced angiogenesis and vascular hyperpermeability. FASEB J. 2003;17:262–264. 10.1016/j.bbrc.2009.05.099 1992, 267, 10931, 10.1016/S0021-9258(19)49853-0