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Antibody-drug conjugate (ADC) consists of a monoclonal antibody (mAb), a cytotoxic agent, and a linker, combining the target specificity of the mAb with the highly potent killing effect of the cytotoxic payload. Antibodies in ADCs determine the plasma circulation duration, immunogenicity, immune function, and target specificity of ADCs. Payloads are the components that exert cytotoxic effects on the cells targeted by the ADC, which are often powerful chemotherapeutic agents including tubulin inhibitors (e.g., auristatins and maytansinoids), DNA-damaging agents (e.g., carbamycin analogues), and topoisomerase inhibitors (e.g., camptothecin and analogues). The function of a linker in ADC is to ensure that the payload remains bound to the antibody during cycling and is released at the target site. Effective linker design must achieve an equilibrium between the necessity for long-term stability of the ADC in circulation and effective cleavage when internalized into the target cell. Linkers can be cleavable or non-cleavable. Non-cleavable linkers contain stable bonds and can withstand proteolytic degradation and release of cytotoxic payloads only occurs after internalization of the conjugate and full breakdown of antibody by lysosomal proteolytic degradation. Because of their high stability, non-cleavable linkers can increase the therapeutic window by minimizing off-target toxicity. In addition, non-cleavable linkers can modify the chemistry of small molecules to enhance transporter affinity and improve the efficacy of ADCs. Cleavable linkers depend on the inherent properties of target cells for selective release of cytotoxic payloads from ADCs and can be influenced by external pH, lysosomal proteases, or glutathione reduction.

A drug-linker conjugate consists of a cytotoxic agent and an appropriate linker. Amerigo Scientific offers a wide range of drug-linker conjugates that can be linked with monoclonal antibodies to prepare ADCs.