Antibody-drug conjugate, and intermediate thereof, preparation method therefor, and application thereof

An antibody-drug conjugate;

• the antibody-drug conjugate has a structure shown in formula I;
• wherein Ab is a HER3 antibody A or a variant of the HER3 antibody A;
• the amino acid sequence of the light chain in HER3 antibody A is shown in SEQ ID NO:
• 1, and the amino acid sequence of the heavy chain is shown in SEQ ID NO:
• 2;
• the amino acid sequence of the light chain in the variant of HER3 antibody A is shown in SEQ ID NO:
• 1;
• the amino acid sequence of the heavy chain in the variant of HER3 antibody A is the amino acid sequence shown in SEQ ID NO:
• 2 having one or more than one site mutation of E233P, L234V, L234F, L235A, L235E, or P331S;
• m is 2 to 8;
• D is a cytotoxic drug topoisomerase inhibitor;
• the cytotoxic drug topoisomerase inhibitor is
• R2 and R5 are each independently H, C1-C6 alkyl or halogen;
• R3 and R6 are each independently H, C1-C6 alkyl or halogen;
• R4 and R7 are each independently C1-C6 alkyl;
• R1 is C1-C6 alkyl substituted by one R1-3S(O)2—, R1-3 is C1-C6 alkyl;
• L1 is independently one or more than one of phenylalanine residue, alanine residue, glycine residue, glutamic acid residue, aspartic acid residue, cysteine residue, histidine residue, isoleucine residue, leucine residue, lysine residue, methionine residue, proline residue, serine residue, threonine residue, tryptophan residue, tyrosine residue, and valine residue;
• p is 2;
• L2 is
• wherein n is independently 1 to 12, the c-terminal is connected to L1 through a carbonyl group, and the f-terminal is connected to the d-terminal of L3;
• L3 is
• wherein the b-terminal is connected to the Ab, and the d-terminal is connected to the f-terminal of L2.