Thalidomide-O-amido-C8-NH2 (TFA) is a premium E3 Ligase Ligand-Linker Conjugate specifically designed for use in PROTAC (Proteolysis Targeting Chimera) drug development. This compound integrates the cereblon (CRBN) ligand thalidomide with a C8 amide-based linker, terminating in a primary amine (NH2), all provided as a trifluoroacetate (TFA) salt. Thalidomide-O-amido-C8-NH2 enables researchers to create highly effective PROTAC molecules by facilitating the recruitment of the CRBN E3 ubiquitin ligase, a crucial step in targeted protein degradation. As a critical tool in the synthesis of next-generation therapeutics, this conjugate supports rapid assembly of PROTACs directed toward challenging disease-related proteins, accelerating drug discovery in oncology, neurodegeneration, and other therapeutic areas. Ideal for medicinal chemistry labs and pharmaceutical R&D, Thalidomide-O-amido-C8-NH2 (TFA) ensures high purity and robust performance in advanced protein degradation research.
Structure of 1950635-16-1
* For research and manufacturing use only. Not for human or clinical use.
| Size | Price | Stock | Quantity |
|---|---|---|---|
| 100 mg | $469 | In stock |
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Background Introduction
Thalidomide-O-amido-C8-NH2 (TFA) is a specialized E3 ligase ligand-linker conjugate, frequently used in the research and development of PROTACs (Proteolysis Targeting Chimeras). Serving as a thalidomide-based cereblon (CRBN) ligand functionalized with an eight-carbon linker ending in a primary amine, this compound offers versatile conjugation possibilities for generating targeted protein degraders. The TFA salt form enhances its solubility and stability, making it suitable for various medicinal chemistry and chemical biology applications.
Mechanism
Thalidomide-O-amido-C8-NH2 (TFA) acts as a bifunctional building block, designed to recruit the E3 ubiquitin ligase cereblon (CRBN) within PROTAC constructs. The thalidomide moiety binds specifically to CRBN, while the C8 amido linker provides optimal spacing and flexibility for attaching diverse target protein ligands through the terminal amine group. Once tethered to a ligand for the protein of interest, the resulting PROTAC can induce proximity-driven ubiquitination and subsequent proteasomal degradation of the target protein, thereby facilitating selective and catalytic protein knockdown.
Applications
Thalidomide-O-amido-C8-NH2 (TFA) is widely used in the design, synthesis, and optimization of PROTACs for targeted protein degradation studies. Its extended amide linker and reactive primary amine enable customizable conjugations with various warheads or payloads, allowing researchers to tailor PROTACs for different targets. Key applications include exploratory drug discovery, mechanistic studies on protein homeostasis, and functional validation of potential therapeutic protein targets in oncology, immunology, and neurodegenerative research. The compound’s utility also extends to generating molecular glues, studying E3 ligase biology, and developing novel therapeutic modalities in the field of targeted protein degradation.
Thalidomide-O-amido-C8-NH2 (TFA) serves as an essential E3 Ligase Ligand-Linker Conjugate in PROTACs, facilitating targeted protein degradation by linking a ligand to a protein of interest. This molecule enhances specificity and efficiency in degrading unwanted proteins, crucial for therapeutic research and drug development. The following provides a detailed description of this molecule.
Linker: The linker in Thalidomide-O-amido-C8-NH2 (TFA) is an aliphatic chain with eight carbon atoms, providing moderate flexibility. This flexibility allows optimal positioning of the ligand while maintaining a stable connection. The linker is non-cleavable, ensuring persistent interaction with the target protein.
Ligand: The ligand component of this molecule is derived from thalidomide, a well-characterized E3 ligase ligand. It features a glutarimide ring structure, which is crucial for binding to the cereblon E3 ubiquitin ligase, facilitating the ubiquitination and subsequent degradation of target proteins.
Reactive Site: The reactive site of Thalidomide-O-amido-C8-NH2 (TFA) is the terminal amine group. This site effectively couples with carboxylic acid groups on the target protein ligand through amide bond formation, offering robust and stable conjugation.
Recommended Target Protein Ligand: A suitable warhead for this conjugate is one containing a carboxylic acid functional group, which allows efficient amide bond formation with the terminal amine of the linker. This compatibility enhances the molecule's utility in targeting proteins for degradation, making it ideal for research applications focused on elucidating protein function and validating therapeutic targets.
* 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
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