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) compound of the following formula:
wherein the compound is ((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3′, 4′: 6, 7]indolizino[1,2-b]quinolin-9-yl 4-(2-(5-(3-(2,4-dihydroxy-5-isopropylphenyl)-5-hydroxy-4H-1,2,4-triazol-4-4yl)-1H-indol-1-yl) ethyl)piperidine-1-carboxylate.
2. A pharmaceutical composition comprising a therapeutically effective amount of the SDC-TRAP of claim 1 , and at least one pharmaceutical excipient.
3. A method of treating cancer in a subject in need thereof comprising administering a therapeutically effective amount of the SDC-TRAP compound of claim 1 , thereby treating the subject.
4. A kit comprising at least one SDC-TRAP and instruction for administering an effective amount of at least one SDC-TRAP to the subject, wherein the SDC-TRAP is the SDC TRAP of claim 1 .
5. The method of claim 3 , wherein the cancer is colorectal cancer.
6. The method of claim 3 , wherein the cancer is breast cancer.
7. The method of claim 3 , wherein the cancer is small cell lung cancer.
8. The method of claim 3 , wherein the cancer is sarcoma.
9. The method of claim 3 , wherein the cancer is pancreatic cancer.