Targeted therapeutics

Abstract

The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

We claim: 
     
         1 . A binding moiety-drug conjugate (SDC-TRAP) comprising a binding moiety and an effector moiety,
 wherein the binding moiety binds to Hsp90,   wherein the effector moiety is a cytotoxic agent selected from the group consisting of LY2801653, LY2835219, LY2606368, LY2874455, LY2090314, LY2940680, LY2784544, LY2228820, LY2157299, LY2603618, LY353381, trimetrexate, and a derivative thereof, and   wherein the binding moiety and the effector moiety are covalently attached.   
     
     
         2 . The SDC-TRAP of  claim 1 , wherein the binding moiety is an Hsp90 ligand or a prodrug thereof. 
     
     
         3 . The SDC-TRAP of  claim 2 , wherein the Hsp90 ligand is an Hsp90 inhibitor. 
     
     
         4 . The SDC-TRAP of  claim 3 , wherein the Hsp90 inhibitor is selected from the group consisting of ganetespib, geldanamycins, macbecins, tripterins, tanespimycins, radicicols, and a derivative thereof. 
     
     
         5 . The SDC-TRAP of  claim 1 , wherein the binding moiety and the effector moiety are covalently attached by a linker. 
     
     
         6 . A pharmaceutical composition comprising a therapeutically effective amount of at least one SDC-TRAP of  claim 1 , and at least one pharmaceutical excipient. 
     
     
         7 . A kit for imaging, diagnosing, and/or selecting a subject comprising at least one SDC-TRAP of  claim 1  and instruction for administering an effective amount of at least one SDC-TRAP of  claim 1  to the subject, thereby imaging, diagnosing, and/or selecting the subject. 
     
     
         8 . A method for treating a subject having a cancer comprising administering a therapeutically effective amount of at least one SDC-TRAP to the subject, thereby treating the cancer,
 wherein the SDC-TRAP comprises the SDC-TRAP of  claim 1 .   
     
     
         9 . A method for treating a subject having chronic bronchitis comprising administering a therapeutically effective amount of at least one SDC-TRAP to the subject, thereby treating the chronic bronchitis,
 wherein the SDC-TRAP comprises the SDC-TRAP of  claim 1 .   
     
     
         10 . A method for treating a subject having asthma comprising administering a therapeutically effective amount of at least one SDC-TRAP to the subject, thereby treating the asthma,
 wherein the SDC-TRAP comprises the SDC-TRAP of  claim 1 .   
     
     
         11 . A method for treating a subject having actinic keratosis comprising administering a therapeutically effective amount of at least one SDC-TRAP to the subject, thereby treating the actinic keratosis,
 wherein the SDC-TRAP comprises the SDC-TRAP of  claim 1 .