The current invention concerns compounds, such as antibody-conjugates, with an enhanced selectivity of payload release inside a tumour or in the tumour microenvironment versus payload release in circulation or in healthy cells. The enhanced selectivity is achieved by incorporation of a cleavable linker that requires two consecutive mechanisms for release of the payload. The compounds according to the invention have structure (1) or a salt thereof, wherein AB is an antibody or a reactive moiety capable of reacting with a functional group on an antibody, L1 and L2 are linkers, moiety I contains an activating group and an aromatic ring, X is O or N and D is the payload. The invention further concerns application of these compounds in for example a method of targeting a cell and a method for enhancing the bystander effect of an amino-containing payload. The invention also concerns the payloads that may be released from the compounds according to the invention.
当前的发明涉及化合物,如
抗体结合物,其在肿瘤内或肿瘤微环境中释放药物载体的选择性增强,相对于在循环中或健康细胞中释放药物载体。通过引入需要两个连续机制释放药物载体的可切割连接剂,实现了增强的选择性。根据该发明的化合物具有结构(1)或其盐,其中AB是
抗体或能够与
抗体上的功能基团发生反应的反应性基团,L1和
L2是连接剂,基团I包含活化基团和芳香环,X为O或N,D为药物载体。该发明还涉及这些化合物在例如靶向细胞的方法和增强含
氨基药物载体的旁观效应的方法中的应用。该发明还涉及这些化合物中可能释放的药物载体。