Description

• Application: Protein degrader builiding block Pomalidomide-PEG2-butyl Iodide enables the synthesis of molecules for targeted protein degradation and PROTAC (proteolysis-targeting chimeras) technology. This conjugate contains a Cereblon (CRBN)-recruiting ligand, a linker with both hydrophobic and hydrophilic moieties, and a pendant iodoalkane for reactivity with a nucleophilic group on a target ligand. Because even slight alterations in ligands and crosslinkers can affect ternary complex formation between the target, E3 ligase, and PROTAC, many analogs are prepared to screen for optimal target degradation. When used with other protein degrader building blocks with a pendant iodo group, parallel synthesis can be used to more quickly generate PROTAC libraries that feature variation in crosslinker length, composition, and E3 ligase ligand.
• Other Notes: Technology Spotlight: Degrader Building Blocks for Targeted Protein DegradationPortal: Building PROTAC® Degraders for Targeted Protein DegradationTargeting the C481S Ibrutinib-Resistance Mutation in Bruton′s Tyrosine Kinase Using PROTAC-Mediated DegradationModular PROTAC Design for the Degradation of Oncogenic BCR-?ABLTargeted Protein Degradation by Small MoleculesSmall-Molecule PROTACS: New Approaches to Protein DegradationTargeted Protein Degradation: from Chemical Biology to Drug DiscoveryImpact of linker length on the activity of PROTACs
• Legal Information: PROTAC is a registered trademark of Arvinas Operations, Inc., and is used under license