Drug-Linker Conjugates

rug-linker complexes consist of two parts: a highly toxic drug which is a small molecule that interacts with intracellular targets and functions as agents to block or disrupt crucial cellular metabolic pathways and eventually lead to cell death, and a linker which facilitates the conjugation of ADC toxins to antibodies and in the meantime, dictates the release mechanism of an ADC. Pre-assembled drug-linker complexes can conjugate to ready-to-go antibody to speed up new antibody-drug conjugate (ADC) development processes.The Drug-Linker Conjugates can expand the utility of mAbs and improve their potency and effectiveness; the antibodies are thus used as a means to target and delivery a toxic payload to the selected diseased tissue. 
The site-specific conjugations of Drug-Linker to an antibody may involve genetic engineering of the mAb to introduce discrete, available cysteines or non-natural amino acids with an orthogonally-reactive functional group handle such as an aldehyde, ketone, azido, or alkynyl tag. These site-specific approaches not only increase the homogeneity of ADCs but also enable novel bio-orthogonal chemistries that utilize reactive moieties other than thiol or amine. The cytotoxic drug, monomethyl auristatin E (MMAE), is conjugated to the three trastuzumab variants using a protease cleavable linker and shows in vivo therapeutic efficacy. 

Drug-Linker Conjugates