ADC Linkers

ADC linkers are one of the three main components of the antibody drug conjugates (ADC) that connect an antibody with a potent drug (payload) through a chemical bond.

ADC linkers play key roles in determining the overall success of the Antibody Drug Conjugates. One of the main challenges in developing a safe and effective ADC drug is the assembly of a desirable chemical linker between cytotoxic payload and mAb. A well-designed ADC linker can help the antibody to selectively deliver and accurately release the cytotoxic drug at tumor sites. It also plays critical roles in an ADCs' stability during preparation, storage, and systemic circulation. A stable ADC drug ensures that less cytotoxic payloads fall off before reaching tumor cells, increasing safety, and limiting dose.

There are two main categories of ADC linkers in current ADC drugs, cleavable linkers and non-cleavable linkers.

1.         Cleavable linker: The linker may be cleavable. Here, a chemical bond (or multiple chemical bonds) between the payload and the antibody attachment site (usually an amino acid) will be cleaved intracellularly. The cleavable linker can be degraded under different pH values or the action of intracellular enzymes to achieve the separation of chemical drugs from antibodies. Adcetris uses this kind of linker. Since the chemical may escape from the target cell after the drug is released, the drug can also kill the adjacent tissue of the target cell.

2.         Noncleavable linker: The noncleavable linker maintains the coupling integrity of the antibody and the chemical drug throughout the entire drug action process. The final active metabolite, released by ADC in the lysosome after complete hydrolysis by the protease, contains the payloads and all the constituent elements of the linker still connected to the amino acid residues of the antibody, which is usually lysine or cysteine residue. Kadcyla uses this kind of non-cleavable linker, so the drug will eventually degrade into a mixture of amino acids, antibodies, chemicals and other components after entering the target cells.

LEAPChem offers a wide range of different cleavable linkers, non-cleavable linkers, linker payload, and other linkages to empower our customer’s advanced research worldwide. These compounds feature great aqueous solubility, and a broad selection of functional groups to choose from.