TARGETED THERAPEUTICS

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.

HSP90 INHIBITOR DRUG CONJUGATES

The present invention provides Hsp90 drug conjugates (HDCs) comprising an Hsp90 ligand or prodrug thereof, a linker moiety and a payload moiety. The invention also provides methods for treating a disease or disorder in a subject, for example cancer, with an HDC. 1. An Hsp90 drug conjugate (HDC) comprising an Hsp90 ligand or prodrug thereof , a linker moiety and a payload moiety.2. The HDC of claim 1 , wherein the Hsp90 ligand is an Hsp90 inhibitor.3. The HDC of claim 2 , wherein the Hsp90 inhibitor is ganetespib claim 2 , AUY-922 or AT-13387.46.-. (canceled)7. The HDC of claim 1 , wherein the payload moiety is an auristatin.8. The HDC of claim 7 , wherein the auristatin is Monomethyl auristatin E (MMAE).9. The HDC of claim 8 , wherein the HDC is selected from the group consisting of SDC-TRAP-0535 to SDC-TRAP-0540.10. The HDC of claim 1 , wherein the payload moiety is selected from the group consisting of: imids claim 1 , proteasome inhibitors claim 1 , PARP inhibitors claim 1 , cell cycle inhibitors claim 1 , alkylating agents claim 1 , anthracyclines claim 1 , antimetabolites claim 1 , epigenetic modifiers claim 1 , hormonal therapy claim 1 , microtubule stabilizers claim 1 , platinums and tyrosine kinase inhibitors.11. The HDC of claim 1 , wherein the payload moiety is an ERK kinase inhibitor.12. The HDC of claim 11 , wherein the ERK kinase inhibitor is BVD-523.13. The HDC of claim 12 , wherein the HDC is selected from the group consisting of SDC-TRAP-0507 to SDC-TRAP-0523.14. The HDC of claim 1 , wherein the payload moiety is a MEK inhibitor.15. The HDC of claim 14 , wherein the MEK inhibitor is TAK-733.16. The HDC of claim 15 , wherein the HDC is selected from the group consisting of SDC-TRAP-0524 to SDC-TRAP-0534.17. (canceled)18. The HDC of claim 1 , wherein the linker moiety and the payload moiety are covalently attached.19. The HDC of claim 1 , wherein the Hsp90 ligand and the linker moiety are covalently attached.20. The HDC of claim 1 , wherein the linker ...

TARGETED THERAPEUTICS

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. 1. A binding moiety-drug conjugate (SDC-TRAP) comprising a binding moiety and an effector moiety , wherein the binding moiety is an Hsp90 ligand or prodrug thereof.2. The SDC-TRAP of claim 1 , wherein the Hsp90 ligand is an Hsp90 inhibitor.3. The SDC-TRAP of claim 2 , wherein the Hsp90 inhibitor is selected from the group consisting of geldanamycins claim 2 , macbecins claim 2 , tripterins claim 2 , tanespimycins claim 2 , radicicols claim 2 , AUY-922 claim 2 , VER-82160 claim 2 , AT-13387 claim 2 , Geldanamycin claim 2 , SNX-5422 claim 2 , BI113028 claim 2 , and MPC-3100.4. The SDC-TRAP of claim 1 , wherein the effector moiety is a therapeutic moiety.5. The SDC-TRAP of claim 4 , wherein the therapeutic moiety is a cytotoxic moiety.6. The SDC-TRAP of claim 5 , wherein the cytotoxic moiety is dasatinib claim 5 , SN-38 claim 5 , bendamustine claim 5 , a VDA claim 5 , doxorubicin claim 5 , pemetrexed claim 5 , vorinostat claim 5 , lenalidomide claim 5 , irinotecan claim 5 , ganetespib claim 5 , docetaxel claim 5 , 17-AAG claim 5 , 5-FU claim 5 , abiraterone claim 5 , crizotinib claim 5 , KW-2189 claim 5 , BUMB2 claim 5 , DC1 claim 5 , CC-1065 claim 5 , adozelesin claim 5 , or fragment thereof.7. The SDC-TRAP of claim 1 , wherein the molecular weight of the SDC-TRAP is less than about 1600 Daltons claim 1 ...

Targeted therapeutics having an hsp90 ligand as binding moiety

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 and therapeutic methods 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 which is an Hsp90 ligand and an effector moiety. The therapeutic uses include the treatment of cancer, chronic bronchitis, asthma, and actinic keratosis.

Hsp90 inhibitor drug conjugates

The application concerns an Hsp90 drug conjugate (HDC) comprising an Hsp90 ligand or prodrug thereof, a linker moiety and a payload moiety, wherein the payload moiety is an ERK kinase inhibitor.

Hsp90 inhibitor drug conjugates