Macrocyclic Drug Conjugate, and Preparation Method Therefor and Use Thereof
AssigneeSichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
InventorsQiang TIAN, Yitao ZHANG, Dong LONG, Jian YE, Qin ZHOU, Hu LONG, Yu YANG, Xiaoxi YUAN, Hongmei SONG, Junyou GE
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Abstract
Provided are a macrocyclic drug conjugate, and a preparation method therefor and the use thereof. The macrocyclic drug conjugate has a structure as shown in formula Ab-[M-L-E-D]x. The antibody-drug conjugate has a good targeted killing effect on solid tumors such as gastric cancer, breast cancer, lung cancer and urothelial carcinoma.
Claims26
An antibody-drug conjugate, which has a structure represented by the formula Ab-[M-L-E-D]x, wherein:
- Ab represents an antibody or antigen-binding fragment thereof capable of specifically binding to epidermal growth factor receptor 2 (Her2), a member of the ErbB family of receptor tyrosine kinases:
- M represents a linker moiety connecting to the antibody or antigen-binding fragment thereof,
- L represents a structural fragment connecting the linker moiety M and E;
- E represents a structural fragment connecting L and D;
- D represents a cytotoxic drug fragment;
- x is 1 to 10.
-24. (canceled)
A compound having the following structure, or a salt, a stereoisomer, a tautomer or an isotopically labeled compound thereof:
A compound having the following structure, or a salt, a stereoisomer, a tautomer or an isotopically labeled compound thereof:
- wherein
- PG1 is each independently H or a carboxyl protecting group, such as C1-6 alkyl, allyl, benzyl, 2,4-dimethoxybenzyl, p-methoxybenzyl, methoxyethoxymethyl, pentafluorophenyl, 4-p-methylbenzyloxybenzyl;
- PG2 is each independently H or an amino protecting group, for example, an alkoxycarbonyl amino protecting group, such as benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc), fluorenylmethoxycarbonyl (Fmoc), allyloxycarbonyl (Alloc), trimethylsilylethoxycarbonyl (Teoc), methyl(or ethyl)oxycarbonyl;
- an acyl amino protecting group, such as phthaloyl (Pht), p-toluenesulfonyl (Tos), trifluoroacetyl (Tfa), o-(p-)nitrobenzenesulfonyl (Ns), pivaloyl, benzoyl, tert-butyloxycarbonyl, 9-fluorenylmethoxycarbonyl, allyloxycarbonyl, trichloroethoxycarbonyl, trimethylsilylethoxycarbonyl, benzyloxycarbonyl, p-toluenesulfonyl, p-nitrobenzenesulfonyl, trifluoroacetyl, methoxycarbonyl, or ethoxycarbonyl;
- an alkyl amino protecting group, such as trityl (Trt), 2,4-dimethoxyhenzyl (Dmb), 4-methoxyhenzyl (PMVB), benzyl (Bn).
(canceled)
Dependencies are inferred from the claim text.