Proteolysis Targeting Chimeric Molecules: Tuning Molecular Strategies for a Clinically Sound Listening.

ABSTRACT: From seminal evidence in the early 2000s, the opportunity to drive the specific knockdown of a protein of interest (POI) through pharmacological entities called Proteolysis Targeting Chimeric molecules, or PROTACs, has become a possible therapeutic option with the involvement of these compounds in clinical trials for cancers and autoimmune diseases. The fulcrum of PROTACs pharmacodynamics is to favor the juxtaposition between an E3 ligase activity and the POI, followed by the ubiquitination of the latter and its degradation by the proteasome system. In the face of an apparently modular design of these drugs, being constituted by an E3 ligase binding moiety and a POI-binding moiety connected by a linker, the final structure of an efficient PROTAC degradation enhancer often goes beyond the m

SUBMITTER: Pedrucci F 

PROVIDER: S-EPMC9223854 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature