Methods and compositions for degradation and/or inhibition of HER-family tyrosine kinases
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 joi...
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creator | Rosen, Neal Kuduk, Scott D Danishefsky, Samuel J Zheng, Furzhong F Sepp-Lorenzino, Laura Ouerfelli, Ouatek |
description | 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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title | Methods and compositions for degradation and/or inhibition of HER-family tyrosine kinases |
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