ANTIBODY-DRUG CONJUGATE

摘要

As an antitumor drug which is excellent in terms of antitumor effect and safety, there is provided an antibody-drug conjugate in which an antitumor compound represented by the following formula is conjugated to an antibody via a linker having a structure represented by the following formula:;-L1-L2-LP-NH—(CH2)n1-La-Lb-Lc-;wherein the antibody is connected to the terminal of L1, and the antitumor compound is connected to the terminal of Lc with the nitrogen atom of the amino group at position 1 as a connecting position.

主权项

1. An antibody-drug conjugate wherein an antitumor compound represented by the following formula: is conjugated to an antibody via a linker having a structure represented by the following formula:
-L1-L2-LP-NH—(CH2)n1-La-Lb-Lc- wherein the antibody is connected to the terminal of L1, the antitumor compound is connected to the terminal of Lc with the nitrogen atom of the amino group at position 1 as the connecting position, wherein n1 represents an integer of 0 to 6, L1 represents -(Succinimid-3-yl-N)—(CH2)n2-C(═O)—, —CH2—C(═O)—NH—(CH2)n3-C(═O)—, —C(O)-cyc.Hex(1,4)-CH2—(N-ly-3-diminiccuS)-, or —C(═O)—(CH2)n4-C(═O)—,
wherein n2 represents an integer of 2 to 8, n3 represents an integer of 1 to 8, n4 represents an integer of 1 to 8, L2 represents —NH—(CH2—CH2—O)n5-CH2—CH2—C(═O)—, —S—(CH2)n6-C(═O)—, or a single bond,
wherein n5 represents an integer of 1 to 6, n6 represents an integer of 1 to 6, LP represents a peptide residue consisting of 2 to 7 amino acids, La represents —C(═O)—NH—, —NR1—(CH2)n7-, —O—, or a single bond,
wherein n7 represents an integer of 1 to 6, R1 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, —(CH2)n8-COOH, or —(CH2)n9-OH, n8 represents an integer of 1 to 4, n9 represents an integer of 1 to 6, Lb represents —CR2(—R3)—, —O—, —NR4—, or a single bond,
wherein R2 and R3 each independently represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, —(CH2)na-NH2, —(CH2)nb-COOH, or —(CH2)nc-OH, R4 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, na represents an integer of 0 to 6, nb represents an integer of 1 to 4, na represents an integer of 1 to 4, provided that when na is 0, R2 and R3 are not the same as each other, Lc represents —CH2— or —C(═O)—, -(Succinimid-3-yl-N)— has a structure represented by the following formula: which is connected to the antibody at position 3 thereof and is connected to a methylene group in the linker structure containing this structure on the nitrogen atom at position 1, —(N-ly-3-diminiccuS)- has a structure represented by the following formula: which is connected to L2 at position 3 thereof and is connected to a methylene group in the linker structure containing this structure on the nitrogen atom at position 1, cyc.Hex(1,4) represents a 1,4-cyclohexylene group, and when L2 is —S—(CH2)n6-C(═O)—, L1 is —C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-diminiccuS)-.