4-((2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

Description

Pomalidomide-PEG3-C2-NH2 is a Pomalidomide-based cereblon ligand with a linker, which is a useful precursor for synthesis of PROTAC degraders. Targeted protein degradation (TPD) is an emerging therapeutic modality with the potential to tackle disease-causing proteins that have historically been highly challenging to target with conventional small molecules. PROTAC degraders are usually heterobifunctional small molecules consisting of two ligands joined by a linker: one ligand recruits and binds a protein of interest (POI) while the other recruits and binds an E3 ubiquitin ligase. Simultaneous binding of the POI and ligase by the PROTAC induces ubiquitylation of the POI and its subsequent degradation by the ubiquitin–proteasome system (UPS), after which the PROTAC is recycled to target another copy of the POI.

Uses

Pomalidomide-PEG3-C2-NH2 is a synthesized E3 ligase ligand-linker conjugate that incorporates the Pomalidomide based cereblon ligand and 3-unit PEG linker used in PROTAC technology.

IC 50

Cereblon

References

[1] Li Y, et al. Discovery of MD-224 as a First-in-Class, Highly Potent, and Efficacious Proteolysis Targeting Chimera Murine Double Minute 2 Degrader Capable of Achieving Complete and Durable Tumor Regression. J Med Chem. 2019 Jan 24;62(2):448-466. DOI:10.1021/acs.jmedchem.8b00909