Linker, linker-containing antibody drug conjugate, and preparation method therefor and use thereof
AssigneesChengdu Chipscreen Newway Biosciences Co., Ltd., Shenzhen Chipscreen Biosciences Co., Ltd.
InventorsLi LIU, Gang LIU, Bin LIU, Desi PAN, Xianping LU
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Abstract
Provided is a linker-containing antibody drug conjugate. Also involved are a pharmaceutical composition comprising the antibody conjugate, a use of a linker, and a use of the antibody conjugate in the preparation for a drug for preventing and/or treating diseases.
Claims15
A compound represented by formula I, a stereoisomer thereof, a tautomer thereof, a pharmaceutically acceptable salt thereof, a deuterated compound thereof, or a solvate thereof:
- wherein
- L1 is selected from
- preferably, the carbon end of L1 is linked to the N of succinimide, and the carbonyl end of L1 is linked to L2;
- m and t are each independently selected from:
- 0, 1, 2, 3, 4, 5, 6, 7, and 8;
- q is 0, 1, 2, or 3;
- p is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15;
- X is selected from:
- CH2, O, and NH;
- L2 is absent, or is an amino acid residue, or is a peptide residue consisting of 2-10 amino acid residues;
- preferably, the amino end of L2 is linked to L1, and the carbonyl end of L2 is linked to L3;
- preferably, the amino acid includes, but is not limited to, phenylalanine (F), glycine (G), valine (V), lysine (K), serine (S), glutamic acid (E), asparagine (N), arginine (R), alanine (A), citrulline, and cysteine (C);
- L3 is absent, or is selected from
- preferably, the amino end of L3 is linked to L2, and the carbonyl end or carbon end of L3 is linked to D;
- D is a histone deacetylase inhibitor drug selected from a thiol-based histone deacetylase inhibitor, a hydroxamic acid-based histone deacetylase inhibitor, and a benzamide-based histone deacetylase inhibitor.
A ligand-drug conjugate represented by formula II, a stereoisomer thereof, a tautomer thereof, a pharmaceutically acceptable salt thereof, a deuterated compound thereof, or a solvate thereof:
- wherein
- Ab is a ligand selected from a protein, an antibody, a polypeptide, an enzyme, and a small molecule;
- n is a number between 0.5 and 8.5;
- for example, n is a number between 0.8 and 5, a number between 1 and 4, a number between 2 and 6, a number between 3 and 7, a number between 4 and 8, a number between 3.5 and 8.5, a number between 3.5 and 4.5, or a number between 6.5 and 8.5;
- preferably, n is about 2, 3, 4, 5, 6, 7, or 8;
- more preferably, n is about 3, 4, 5, 6, 7, or 8;
- L1 is selected from
- preferably, the carbon end of L1 is linked to the N of succinimide, and the carbonyl end of L1 is linked to L2;
- m and t are each independently selected from:
- 0, 1, 2, 3, 4, 5, 6, 7, and 8;
- q is 0, 1, 2, or 3;
- p is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15;
- X is selected from:
- CH2, O, and NH;
- L2 is absent, or is an amino acid residue, or is a peptide residue consisting of 2-10 amino acid residues;
- preferably, the amino end of L2 is linked to L1, and the carbonyl end of L2 is linked to L3;
- preferably, the amino acid includes, but is not limited to, phenylalanine (F), glycine (G), valine (V), lysine (K), serine (S), glutamic acid (E), asparagine (N), arginine (R), alanine (A), citrulline, and cysteine (C);
- L3 is absent, or is selected from
- preferably, the amino end of L3 is linked to L2, and the carbonyl end or carbon end of L3 is linked to D;
- D is a histone deacetylase inhibitor drug selected from a thiol-based histone deacetylase inhibitor, a hydroxamic acid-based histone deacetylase inhibitor, and a benzamide-based histone deacetylase inhibitor.
Dependencies are inferred from the claim text.