Current Topics in Medicinal Chemistry - Volume 17, Issue 32, 2017

Antibody Drug Conjugates (ADCs) use targeting ability of monoclonal antibodies to deliver potent cytototoxic payloads to their intended target. The linker encompasses a conjugating functionality suitable for attachment to the antibody, a spacer unit that typically incorporates a hydrophilic element and a trigger which releases the potent cytototoxic warhead. Understanding the conflicting requirements of ADC design, providi Read More

Overexpressed cell-surface receptors are hallmarks of many disease states and are often used as markers for targeting diseased cells over healthy counterparts. Cell adhesion peptides, which are often derived from interacting regions of these receptor-ligand proteins, mimic surfaces of intact proteins and, thus, have been studied as targeting agents for various payloads to certain cell targets for cancers and autoimmune disea Read More

The recent approval of trastuzumab emtansine (Kadcyla®) and brentuximab vedotin (Adcetris ®) has spurred tremendous investment in new approaches for the targeted delivery of pharmaceutical agents. Targeted delivery approaches, such as Antibody Drug Conjugates (ADCs), typically rely on an endogenous or exogenous “trigger” that results in the release of the pharmacologically active agent at the intended site of a Read More

Non-cleavable linkers are used in a number of different modalities for various reasons, such as linking an active drug moiety to half-life extending molecules, to groups that enable a specific tissue or cell targeting or to facilitate active uptake into target cells. Non-cleavable linkers do not have a designated weak point in their structure that can lead to cleavage by proteases, hydrolases or chemically by pH changes. Consequently, Read More