Thalidomide-O-PEG2-NHS ester is a high-purity E3 Ligase Ligand-Linker Conjugate designed for advanced PROTAC (Proteolysis Targeting Chimera) drug discovery and targeted protein degradation applications. This molecule features a thalidomide-based E3 ligase ligand, linked via a flexible PEG2 (polyethylene glycol) spacer to an N-hydroxysuccinimide (NHS) ester reactive group, allowing efficient conjugation to a wide variety of ligands and amine-containing payloads. The thalidomide moiety specifically recruits the CRBN (cereblon) E3 ubiquitin ligase, a critical component in PROTAC-mediated targeted protein degradation. The PEG2 linker enhances solubility and provides optimal spatial orientation for effective ternary complex formation.
Structure of 2639395-34-7
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Category
E3 Ligase Ligand-Linker Conjugate
Molecular Formula
C24H25N3O11
Molecular Weight
531.47
* For research and manufacturing use only. Not for human or clinical use.
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Thalidomide-O-PEG2-NHS ester is a versatile E3 ligase ligand-linker conjugate designed for targeted protein degradation research, particularly in the development of PROTACs (Proteolysis Targeting Chimeras). This compound consists of a thalidomide derivative, known for binding the cereblon (CRBN) E3 ubiquitin ligase, connected through a biocompatible PEG2 (diethylene glycol) linker to an NHS (N-hydroxysuccinimide) ester reactive group. The presence of the NHS ester allows for highly efficient conjugation to amine groups, facilitating the creation of custom PROTAC molecules.
Mechanism
Thalidomide-O-PEG2-NHS ester functions as a bridge between an E3 ligase and a target protein. The thalidomide moiety selectively binds to the CRBN component of the E3 ubiquitin ligase complex. The PEG2 linker provides spatial flexibility, reducing steric hindrance and improving protein accessibility. The NHS ester reacts with primary amines, such as those present on lysine residues of proteins or small-molecule scaffolds, to form stable amide bonds. This enables the covalent attachment of the E3 ligase ligand to various targeting ligands, supporting the modular assembly of bifunctional PROTAC molecules. Once a PROTAC created with this building block links a target protein to CRBN, it induces ubiquitination and subsequent proteasomal degradation of the target protein.
Applications
Thalidomide-O-PEG2-NHS ester is widely used in the synthesis of PROTAC libraries for drug discovery and targeted protein degradation studies. Its key applications include: 1) Generating CRBN-based PROTACs for selectively degrading disease-related proteins; 2) Functionalizing biomolecules or peptides via conjugation to develop novel chemical biology probes; 3) Facilitating research on E3 ligase substrate specificity and ubiquitin-proteasome system modulation; 4) Exploring next-generation therapeutics for cancer, neurodegeneration, and inflammatory diseases by harnessing targeted protein degradation. This product is an essential building block for researchers developing custom degrader molecules and for accelerating early-stage drug development projects.
• Activated NHS ester allows for rapid and efficient conjugation to amine-containing molecules, streamlining PROTAC assembly.
• PEG2 spacer improves aqueous solubility and flexibility for enhanced CRBN E3 ligase recruitment in PROTAC applications.
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
CAS No.: 2639395-34-7
