Figure 1. The structure and characteristic of an ADC drug [1].
Mechanism of ADC Cytotoxins
ADC cytotoxins (also known as payloads) are cytotoxic agents that induce target cell death in ADCs. They can be divided in two classes based on their mechanism of action, DNA damaging agents and tubulin inhibitors. Among them Calicheamicins, Duocarmycins and Pyrrolobenzodiazepine (PBDs) are DNA minor grove binders, Camptothecins and Daunorubicins/Doxorubicins are topoisomerase inhibitors, which are DNA damaging agents. Auristatins and Maytansinoids are tubulin inhibitors. Except for the listed cytotoxins, there are numbers of traditional cytotoxic agents with similar mechanisms of killing cancer cells and can also be used in the development of ADCs.
The Role of ADC Linkers
ADC linker between the antibody and the cytotoxic drug provides a specific bridge, and thus helps the antibody to selectively deliver the cytotoxic drug to tumor cells and accurately releases the cytotoxic drug at tumor sites. Linkers are mostly classified into two categories: cleavable and noncleavable. Cleavable linkers rely on processes inside the cell to liberate the toxin, such as exposure to acidic conditions in the lysosome, or cleavage by specific proteases within the cell. Noncleavable linkers require proteolytic degradation of the antibody portion of the ADC for release of the cytotoxic molecule, which will retain the linker and the amino acid by which it was attached to the antibody.
ADC Product Overview
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