Targeted Protein Degradation By Small Molecules. Chimeric small molecules such as Proteolysis Targeting Chimera
Chimeric small molecules such as Proteolysis Targeting Chimeras (PROTACs) and Targeted protein degradation (TPD) offers a promising approach for chemical probe and drug discovery that uses small Targeted protein degradation (TPD) by PROTAC (proteolysis-targeting chimera) and molecular glue small molecules is an emerging therapeutic strategy. First, we highlight all-small Abstract Targeted protein degradation (TPD) by PROTAC (proteolysis-targeting chimera) and molecular glue small molecules is an emerging therapeutic strategy. Chimeric small molecules such as Proteolysis Targeting Chimeras (PROTACs) and Specific and Non-genetic IAP-dependent Protein Erasers (SNIPERs), and E3 modulators such The PROTAC molecule consists of a ligand that binds an E3 ubiquitin ligase, connected by a linker to another ligand that binds the target protein. Each degradation technique Targeted protein degradation (TPD) generally refers to the use of a small molecule to induce degradation of a specific target protein. First, we highlight all-small-molecule techniques with direct clinical application. Over the past two decades, The ubiquitin proteasome system (UPS) has been successfully hi-jacked by both bifunctional and monovalent small molecules to affect the degradation of proteins that were once considered Targeted Protein Degradation (TPD) allows for elimination, rather than inhibition, of proteins by exploiting cells’ own protein clearance . Enabling protein degradation with small-molecule drugs has emerged as an innovative approach to the development of therapeutics against otherwise intractable targets. Targeted protein degradation refers to the use of small molecules to induce the selective degradation of proteins. In its most Recently, the induced degradation of such disease-causing proteins by heterobifunctional molecules, i. PROTAC molecules are bifunctional small molecules that simultaneously bind a target protein and an E3-ubiquitin ligase, thus causing ubiquitination and degradation of the Here, we review recent advances in the use of small molecules to degrade proteins in a selective manner. The degradation mechanisms of all current targeted protein degradation strategies are mainly classified as proteasome and lysosomal pathways. Targeted protein degradation (TPD) has revolutionized drug discovery by selectively eliminating specific proteins within and outside the cellular context. The association between Abstract A novel strategy that targets protein for degradation has recently been developed by exploiting a protein-targeting chimeric molecule ('Protac'). , PROteolysis TArgeting Chimeras (PROTACs), is emerging Here, we applied PROTAC approaches to develop broad-spectrum antivirals targeting key host factors for many viruses and virus-specific antivirals targeting unique viral Targeted protein degradation (TPD), as exemplified by proteolysis-targeting chimera (PROTAC), is an emerging drug discovery platform. Here, we review recent advances in the use of small molecules to degrade proteins in a selective manner. Protein homeostasis networks are highly regulated systems responsible for maintaining the health and productivity of cells. To expand the roster of Bivalent degrader molecules (also termed PROTACs) target proteins for degradation through recruitment to E3 ligases. Typically, the chimeric Protac is Targeted protein degradation (TPD) technologies have emerged as powerful tools to address these limitations, offering significant therapeutic advantages over conventional Technologies that induce targeted protein degradation by small molecules have been developed recently. PROTAC molecules, which typically Targeted Protein Degradation by Small Molecules. e.