| abstract |
FIELD: medicine.SUBSTANCE: invention relates to a conjugate of an antibody with a drug for treating a malignant tumor, represented by formula (I), Ab—(L—D), where Ab is an antibody, where the antibody binds to NaPi2b, CD33 or CD22; L is a peptidomimetic linker represented by the following formula —Str— (PM) —Sp—, where Str is an extension covalently attached to Ab; Sp is a bond or a spacer element covalently attached to a drug moiety; PM is a non-peptide chemical moiety selected from the group consisting of:and, Y is selected from C-Calkenyl,each Rindependently represents (C-Calkyl)NHC(O)NH; Rand R, each independently represent H or C-Calkyl; Rand Rtogether can form C-Ccycloalkyl ring; p is integer from 1 to 8; D is a drug moiety of formula (IA) or (IB):(IA)(IB), where Rrepresents a methoxy group, and Ris C-Calkoxy group. Invention also relates to two versions of non-peptide compounds which are suitable for preparing a conjugate, as well as a method of treating myeloid leukemia and a pharmaceutical composition for treating it. Disclosed group of inventions provides non-peptide linkers for ADC, which can be splitted with lysosomal enzymes.EFFECT: disclosed are peptidomimetic compounds and their conjugates of antibodies with drugs.43 cl, 2 dwg, 7 ex |