ADC Linkers

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. 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. There are two main categories of ADC linkers, cleavable linkers and non-cleavable linkers.
Cleavable linkers play a crucial role in the success of antibody-drug conjugates. They are stable in the blood circulation for a long period of time and can efficiently release their payload in the tumor micro-environment, for both the chemically labile linkers and the enzyme cleavable linkers.
Protease-sensitive cleavable linkers use the dominant proteases found in tumor cell lysosomes for recognition and cleavage of a specific peptide sequence in the linker. A commonly used ADC linker is a valine-citrulline (val-cit) dipeptide linker, which can be cleaved by cathepsin B.
Acid-sensitive linkers use a lower pH in the endosomal (pH = 5-6) and lysosomal (pH = 4.8) compartments, in contrast to cytosol (pH = 7.4) to trigger hydrolysis of acid labile groups within a linker such as hydrazone.
Glutathione-sensitive linkers use higher concentrations of intracellular glutathione than in the plasma. This causes disulfide bridges to release the cytotoxin upon reduction by glutathione.
Non-cleavable linkers degrade only when the antibody degrades. The cytotoxic small molecule payload was released during lysosomal degradation of the antibody-drug conjugate within the target cell, thus avoiding non-specific release of the drug.
BroadPharm provides a wide selection of ADC linker including cleavable linkers & non-cleavable linkers, such as Val-Cit, Val-Cit-PAB-PNP, Peptide linkers, Thiol linker, Maleimide linker, Click Chemistry Linker with various functional group.
BroadPharm also offers customer-oriented ADC linker synthesis and services to our customers worldwide, please email to sale@broadpharm.com or call 858-677-6760 for assistance.

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ADC Linkers