申请人:Sugen, Inc.
公开号:US05792771A1
公开(公告)日:1998-08-11
The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction and particularly KDR/FLK-1 receptor signal transduction in order to regulate and/or modulate vasculogenesis and angiogenesis. The invention is based, in part, on the demonstration that KDR/FLK-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of FLK-1. These results indicate a major role for KDR/FLK-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express FLK-1 and the uses of expressed FLK-1 to evaluate and screen for drugs and analogs of VEGF involved in FLK-1 modulation by either agonist or antagonist activities is also described. The invention also relates to the use of the disclosed compounds in the treatment of disorders, including cancer, diabetes, hemangioma and Kaposi's sarcoma, which are related to vasculogenesis and angiogenesis.
本发明涉及有机分子,能够调节酪氨酸激酶信号传导,特别是KDR/FLK-1受体信号传导,以调节和/或调节血管生成和血管新生。该发明部分基于KDR/FLK-1酪氨酸激酶受体表达与内皮细胞相关,并确定血管内皮生长因子(VEGF)为FLK-1的高亲和力配体的论证。这些结果表明KDR/FLK-1在血管生成和血管新生过程中的信号系统中起着重要作用。描述了表达FLK-1的宿主细胞的工程化,以及利用表达的FLK-1评估和筛选参与FLK-1调节的VEGF的药物和类似物,无论是通过激动剂还是拮抗剂活性。该发明还涉及使用所披露的化合物治疗与血管生成和血管新生相关的疾病,包括癌症、糖尿病、血管瘤和卡波西肉瘤。