专利快速检索-快速检索全球专利，免费商用专利数据库-IPRDB

1. 发明申请

WO9943311A2 CONJUGATED SURAMIN OR DERIVATIVES THEREOF WITH PEG, POLYASPARTATE OR POLYGLUTAMATE FOR CANCER TREATMENT 审中-公开
标题翻译：用PEG，聚天冬氨酸或聚谷氨酸盐共轭的SURAMIN或其衍生物用于癌症治疗
公开(公告)号：WO9943311A2
公开(公告)日：1999-09-02
申请号：PCT/US9904336
申请日：1999-02-26
申请人： US HEALTH , WEBB CRAIG P , JEFFERS MICHAEL E , CZERWINSKI GREGORZ , MICHEJDA CHRISTOPHER J , VANDE WOUDE GEORGE F
发明人： WEBB CRAIG P , JEFFERS MICHAEL E , CZERWINSKI GREGORZ , MICHEJDA CHRISTOPHER J , VANDE WOUDE GEORGE F
IPC分类号： A61K47/48 , C09B69/10 , C12Q1/37 , A61K31/185
CPC分类号： C12Q1/37 , A61K47/60 , A61K47/645 , C09B69/106 , G01N2333/9723
摘要： The present invention provides an assay that identifies compounds which inhibit cleavage of HGF/SF by serum proteases such as uPA, and methods in which such compounds are provided to reaction solutions, to cultured cells in vitro, or to a mammal in vivo, to inhibit cleavage of HGF/SF and to inhibit chemical and biological effects resulting from the activation of c-Met receptor by HGF/SF. The invention also provides methods for modifying suramin and suramin-related polysulfonated compounds that inhibit HGF/SF cleavage, by attaching PEG or polyanions such as polyglutamate or polyaspartate to the compounds to reduce cellular uptake of the compounds, thereby reducing their cytotoxicity. Also provided are a pharmaceutical composition containing at least one polysulfonated HGF/SF cleavage-inhibiting compound other than suramin, and a pharmaceutical composition containing at least one HGF/SF cleavage-inhibiting form of suramin or a suramin-related polysulfonated compound that is modified by conjugation to a chemical moiety that reduces uptake of the compound into cells. The present invention further includes methods wherein such pharmaceutical compositions are administered to a mammal with a tumor that is stimulated to grow by HGF/SF, to inhibit the growth or metastasis of the tumor in the mammal.
摘要翻译：本发明提供了鉴定通过血清蛋白酶如uPA来抑制HGF / SF裂解的化合物的测定法，以及将这些化合物提供给反应溶液，体外培养细胞或体内哺乳动物以提供抑制切割HGF / SF并抑制由HGF / SF激活c-Met受体引起的化学和生物效应。本发明还提供了通过将PEG或聚阴离子如聚谷氨酸盐或聚天冬氨酸连接到化合物以减少化合物的细胞摄取从而减少它们的细胞毒性来修饰抑制HGF / SF切割的苏拉明和苏拉明相关多磺化化合物的方法。还提供了一种药物组合物，其含有至少一种除苏拉明以外的多磺化HGF / SF裂解抑制化合物，以及一种药物组合物，该药物组合物含有至少一种被修饰的苏拉明或苏拉明相关多磺化化合物的HGF / SF切割抑制形式缀合至减少化合物向细胞摄取的化学部分。本发明进一步包括这样的方法，其中将这种药物组合物给予患有被HGF / SF刺激生长的肿瘤的哺乳动物，以抑制哺乳动物中肿瘤的生长或转移。

IPRDB

热门服务

关于我们

友情链接

联系方式