Thalidomide-O-amido-C3-COOH

Background Introduction

Thalidomide-O-amido-C3-COOH is an advanced E3 ligase ligand-linker conjugate designed for use in proteolysis targeting chimera (PROTAC) research. This compound combines a thalidomide-derived E3 ligase ligand with a C3 alkyl linker that terminates in a carboxyl group, enabling efficient conjugation to a variety of target protein ligands. As PROTAC technology continues to gain prominence in targeted protein degradation, high-quality E3 ligase ligand-linker intermediates like Thalidomide-O-amido-C3-COOH have become essential tools for drug discovery and functional genomics.

Mechanism

Thalidomide-O-amido-C3-COOH works by leveraging the cellular ubiquitin-proteasome system. When incorporated into PROTACs, the thalidomide moiety specifically binds to the cereblon (CRBN) E3 ubiquitin ligase, while the carboxy-terminated linker allows for chemically attaching a ligand that recognizes the protein of interest. Upon binding both the E3 ligase and the target protein, the resulting PROTAC induces the ubiquitination and subsequent proteasomal degradation of the target protein, offering a catalytic mechanism to remove disease-associated proteins from cells.

Applications

Thalidomide-O-amido-C3-COOH is widely utilized in the development of PROTAC molecules for targeted protein degradation. Researchers can use this E3 ligase ligand-linker intermediate to quickly synthesize new PROTACs aimed at degrading a wide range of proteins, accelerating preclinical drug development and mechanistic studies. Its versatile design enables the generation of diverse PROTAC libraries, facilitating high-throughput screening for novel therapeutics in cancer, neurodegenerative disorders, and other protein dysfunction-related diseases.

• Carboxylic acid-terminated linker enables versatile coupling to target ligands or payloads for PROTAC development.
• Designed for efficient and selective CRBN E3 ligase recruitment in targeted protein degradation applications.