別名

1-((2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-3,6,9,12,15,18-hexaoxahenicosan-21-oic acid,Crosslinker−E3 Ligase ligand conjugate,Protein degrader building block for PROTAC research,Template for synthesis of targeted protein degrader

應(yīng)用

Protein degrader builiding block Pomalidomide-PEG6-CO2H enables the synthesis of molecules for targeted protein degradation and PROTAC (proteolysis-targeting chimeras) technology. This conjugate contains a Cereblon (CRBN)-recruiting ligand and a PEGylated crosslinker with pendant carboxylic acid for reactivity with an amine on the 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 carboxyl group, parallel synthesis can be used to more quickly generate PROTAC libraries that feature variation in crosslinker length, composition, and E3 ligase ligand.

其他說明

TTechnology Spotlight: Degrader Building Blocks for Targeted Protein Degradation

Portal: Building PROTAC? Degraders for Targeted Protein Degradation

Targeted Protein Degradation by Small Molecules

Small-Molecule PROTACS: New Approaches to Protein Degradations

Targeted Protein Degradation: from Chemical Biology to Drug Discovery

Impact of linker length on the activity of PROTACs