AMANITIN ANTIBODY CONJUGATE
A bicyclic octapeptide derivative is conjugated to a corresponding target-binding group by a special chemical structure. The structure of the derivative is stable in blood plasma and decomposes into a drug as an active ingredient in a specific biological environment, thereby maximizing killing effect on target cells and minimizing toxic side effects on non-target cells. The derivative can be used in the treatment of various malignant tumors.
1 . A toxin conjugate as claimed in Structural Formula (I) or its pharmaceutically acceptable salt thereof, comprising a toxin moiety and a biological macromolecule moiety:
wherein:
n=0, 1 or 2,
R 1 corresponds to —H or —OH,
R 2 corresponds to —H or —OH,
R 3 corresponds to —H, —OH or C 1-6 alkyl,
R 4 corresponds to —NH 2 or —OH,
R 5 corresponds to -L-A, wherein A corresponds to the biological macromolecule moiety that is configured to bind to a target, and L corresponds to any chemical structure connecting the toxin moiety and the biological macromolecule moiety, and wherein the toxin moiety comprises an amanitin derivative.
2 . The toxin conjugate as claimed in claim 1 or its pharmaceutically acceptable salt thereof, wherein L comprises a cleavable or non-cleavable chemical structure.
3 . The toxin conjugate as claimed in claim 1 or its pharmaceutically acceptable salt thereof, wherein A comprises an antibody or its antigen-binding fragment or antigen-binding polypeptide thereof.
4 . The toxin conjugate as claimed in claim 1 or its pharmaceutically acceptable salt thereof, wherein -L-A comprises at least one of the following structures:
5 . The toxin conjugate as claimed in claim 1 or its pharmaceutically acceptable salt thereof, wherein L is connected to the toxin moiety via an ester or ether bond.
6 . A drug compound, a comprising the toxin conjugate as claimed in claim 1 or its pharmaceutically acceptable salt thereof.
7 . A method for using the toxin conjugate as claimed in claim 1 or its pharmaceutically acceptable salt thereof, comprising preparing an anti-tumor or anti-cancer drug by incorporating the toxin conjugate or its pharmaceutically acceptable salt thereof.
8 . The method as claimed in claim 7 , wherein the anti-tumor or anti-cancer drug corresponds to comprises an anti-lung cancer drug, an anti-kidney cancer drug, an anti-urinary tract cancer drug, anti-colorectal cancer drug, anti-prostate cancer drug, anti-glioblastoma drug, anti-ovarian cancer drug, anti-pancreatic cancer drug, anti-breast cancer drug, anti-melanoma drug, anti-liver cancer drug, anti-bladder cancer drug, anti-malignant lymphoma drug, anti-leukemia drug, anti-gastric cancer drug or an anti-esophageal cancer drug.