Thalidomide-NH-CH2-COOH trifluoroacetate salt

Background Introduction

Thalidomide-NH-CH2-COOH trifluoroacetate salt is a chemically synthetic E3 ligase ligand-linker conjugate. It is derived from thalidomide, a well-known cereblon (CRBN) E3 ubiquitin ligase modulator, and is specifically designed for constructing PROTAC (Proteolysis Targeting Chimera) molecules. The addition of a carboxylic acid group (-COOH) via an alkyl linker makes this molecule amenable for further conjugation, enabling researchers to connect various target protein binders with an E3 ligase ligand for targeted protein degradation.

Mechanism

Thalidomide-NH-CH2-COOH trifluoroacetate salt works as a vital building block in PROTAC synthesis. The thalidomide scaffold binds selectively to cereblon (CRBN), a substrate receptor of the CUL4 E3 ubiquitin ligase complex. The linker, terminated by a carboxyl (-COOH) group, offers a conjugation site for attaching ligands that recognize other proteins of interest. When incorporated into a PROTAC molecule, this conjugate brings the target protein into proximity with the E3 ligase, leading to ubiquitination and subsequent proteasomal degradation of the target protein. This mechanism enables selective and catalytic protein knockdown with high specificity.

Applications

Thalidomide-NH-CH2-COOH trifluoroacetate salt is widely utilized in medicinal chemistry, chemical biology, and drug discovery research. Its primary application is as a functionalized E3 ligase ligand for PROTAC development, facilitating the targeted degradation of disease-related proteins, including those considered 'undruggable' by conventional inhibitors. This product is suitable for academic and pharmaceutical researchers aiming to explore novel therapeutic modalities, conduct target validation studies, or develop next-generation drugs leveraging protein degradation pathways. Additionally, it can be used to create bifunctional molecules for targeted protein modulation in mechanistic and cellular studies.