Degrader-antibody conjugates. (4th May 2022)

• Record Type: Journal Article
• Authors: Dragovich, Peter S.
• Is Part Of: Chemical Society reviews. Volume 51:Number 10(2022)
• Page Start: 3886
• Page End: 3897
• Publication Date: 2022-05-04
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/d2cs00141a
• Languages: English
• ISSNs: 0306-0012

Abstract

Abstract : This review illustrates the design of antibody conjugates which employ chimeric protein degraders ( i.e., PROTACs) as payloads and summarizes the examples of such entities that are currently known in the scientific and patent literature. Abstract : Degrader-antibody conjugates (DACs) are novel entities that combine a proteolysis targeting chimera (PROTAC) payload with a monoclonal antibody via some type of chemical linker. This review provides a current summary of the DAC field. Many general aspects associated with the creation and biological performance of traditional cytotoxic antibody-drug conjugates (ADCs) are initially presented. These characteristics are subsequently compared and contrasted with related parameters that impact DAC generation and biological activity. Several examples of DACs assembled from both the scientific and the patent literature are utilized to highlight differing strategies for DAC creation, and specific challenges associated with DAC construction are documented. Collectively, the assembled examples demonstrate that biologically-active DACs can be successfully prepared using a variety of PROTAC payloads which employ diverse E3 ligases to degrade multiple protein targets.