发明授权
US07238682B1 Methods and compositions for degradation and/or inhibition of HER-family tyrosine kinases
有权
用于降解和/或抑制HER-家族酪氨酸激酶的方法和组合物
- 专利标题: Methods and compositions for degradation and/or inhibition of HER-family tyrosine kinases
- 专利标题(中): 用于降解和/或抑制HER-家族酪氨酸激酶的方法和组合物
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申请号: US09937192申请日: 2000-04-07
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公开(公告)号: US07238682B1公开(公告)日: 2007-07-03
- 发明人: Neal Rosen , Scott D. Kuduk , Samuel J. Danishefsky , Furzhong F. Zheng , Laura Sepp-Lorenzino , Ouatek Ouerfelli
- 申请人: Neal Rosen , Scott D. Kuduk , Samuel J. Danishefsky , Furzhong F. Zheng , Laura Sepp-Lorenzino , Ouatek Ouerfelli
- 申请人地址: US NY New York
- 专利权人: Sloan-Kettering Institute for Cancer Research
- 当前专利权人: Sloan-Kettering Institute for Cancer Research
- 当前专利权人地址: US NY New York
- 代理机构: Marina Larson & Associates, LLC
- 国际申请: PCT/US00/09512 WO 20000407
- 国际公布: WO00/61578 WO 20011019
- 主分类号: C07D403/02
- IPC分类号: C07D403/02 ; A61K31/395 ; A61P35/00
摘要:
Bifunctional molecules comprising two hsp-binding moieties which bind to hsp90 in the pocket to which ansamycin antibiotics bind connected via a linker are effective for inducing the degradation and/or inhibition of HER-family tyrosine kinases. For example, a compound of two geldanamycin moities joined by a four-carbon linker provides selective degradation of HER-family tyrosine kinases, without substantially affecting other kinases. These compounds can be used for treatment of HER-positive cancers with reduced toxicity, since these compounds potently kill cancer cells but affect fewer proteins than geldanamycin.
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