The ADC linker is one of the three main components of antibody drug conjugates (ADCs), linking the antibody to the effective drug (payload) through chemical bonds. ADC linkers play a key role in determining the overall success of antibody drug conjugates. One of the major challenges in developing safe and effective ADC drugs is to assemble an ideal chemical linker between the cytotoxic payload and the mAb. Well-designed ADC linkers can help the selective delivery of antibodies at the tumor site and the accurate release of cytotoxic drugs.
PROTACs (Proteolytic Targeting Chimeric Molecules) are heterobifunctional protein degraders and are promising targeted therapy candidates for cancer. PROTAC is composed of three parts, one end is connected with the ligand bound by E3 ligase, the other end is connected with the ligand bound by the target protein, and the middle is the linker.
Protac Linkers
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Peptide linkers belong to protease-sensitivity linkers (also called enzymatically cleavable linkers) that have gained significant attention in ADC development due to their superior plasma stability and controled payload release mechanism.
Azides are used in click chemistry, such as copper-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC),and strain-promoted [3+2] azide-alkyne cycloaddition reaction (SPAAC).