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, AUY-922 or AT-13387.
4 .- 6 . (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, proteasome inhibitors, PARP inhibitors, cell cycle inhibitors, alkylating agents, anthracyclines, antimetabolites, epigenetic modifiers, hormonal therapy, microtubule stabilizers, 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 moiety is a cleavable linker.
21 . The HDC of claim 20 , wherein the cleavable linker comprises an enzymatically cleavable linker.
22 . The HDC of claim 1 , wherein the linker is a disulfide linker.
23 . The HDC of claim 1 , wherein the linker is a dipeptide linker.
24 . The HDC of claim 23 , wherein the dipeptide linker is a valine-citrulline (val-cit) linker or a valine-citrulline p-aminobenzylcarbamate (val-cit-PABC) linker.
25 .- 27 . (canceled)
28 . A method of treating a disease or disorder in a subject, comprising administering to the subject an effective amount of the HDC of claim 1 .
29 . A method of treating cancer in a subject, comprising administering to the subject an effective amount of the HDC of claim 1 .
30 . The method of claim 29 , wherein the method further comprises administering an additional anticancer therapy.
31 . A kit comprising the HDC of claim 1 , and instructions for use in treating a disease or disorder.
32 . The kit of claim 31 , wherein the disease or disorder is cancer.