申请人:Sloan-Kettering Institute for Cancer Research
公开号:US06670348B1
公开(公告)日:2003-12-30
Compounds having an ansamycin anitibiotic, or other moiety which binds to hsp90, coupled to a targeting moiety which binds specifically to a protein, receptor or marker can provide effective targeted delivery of the ansamycin antibiotic leading to the degradation of proteins and death of the targeted cells. These compositions may have different specificity than the ansamycin alone, allowing for a more specific targeting of the therapy, and can be effective in instances where the ansamycin alone has no effect. Thus, these compounds provide an entirely new class of targeted chemotherapy agents with application, depending on the nature of the targeting moiety, to treatment of a variety of different forms of cancer. Such agents can further be used to promote selective degradation of proteins associated with the pathogenesis of others diseases, including antigens associated with autoimmune disorders and pathogenic proteins associated with Alzheimer's disease. Exemplary targeting moieties which may be employed in compounds of the invention include testosterone, estradiol, tamoxifen and wortmannin.
具有一种ansamycin抗生素或其他结合到hsp90的基团的化合物,结合到一个能够特异性结合到蛋白质、受体或标记物的靶向基团,可以实现有效的靶向传递ansamycin抗生素,导致蛋白质降解和靶向细胞的死亡。这些组合物可能具有与单独的ansamycin不同的特异性,允许更具体地靶向治疗,并且在ansamycin单独无效的情况下可能有效。因此,这些化合物提供了一类全新的靶向化疗药物,具体应用取决于靶向基团的性质,可用于治疗各种不同形式的癌症。这些药物还可用于促进与其他疾病的发病机制相关的蛋白质的选择性降解,包括与自身免疫性疾病相关的抗原和与阿尔茨海默病相关的致病蛋白。本发明中可能用于化合物的示例性靶向基团包括睾酮、雌二醇、他莫昔芬和沃特曼宁。