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AssigneeSloan-Kettering Institute for Cancer Research
InventorsNeal Rosen, Samuel Danishefsky, Ouathek Ouerfelli, Scott D. Kuduk, Laura Sepp-Lorenzino
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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.
A chemical compound comprising
A method for targeted destruction of cancer cells requiring a protein, receptor or marker for viability, comprising administering to the cells a chemical compound comprising a targeting moiety which specifically binds to a protein, receptor or marker and an hsp-binding moiety which binds to the pocket of hsp90 with which ansamycin antibiotics bind.
A method for targeted destruction of a protein in a cell, comprising administering to the cell a chemical compound comprising a targeting moiety which specifically binds to the protein and an hsp-binding moiety which binds to the pocket of hsp90 with which ansamycin antibiotics bind.
A method for synthesizing a chemical compound comprising a targeting moiety which specifically binds to a receptor or marker and an ansamycin antibiotic, comprising reacting the ansamycin antibiotic with an alkylamine derivative of the targeting moiety.
17-(N-iodoalkyl-N-cyano)-17-demethoxy geldanamycin.
A method for treating cancer comprising administering to a subject suspected to have cancer a therapeutic composition comprising a chemical compound comprising a targeting moiety which specifically binds to a protein, receptor or marker and an hsp-binding moiety which binds to the pocket of hsp90 with which ansamycin antibiotics bind.
Dependencies are inferred from the claim text.