Thalidomide-O-C7-acid

Background Introduction

Thalidomide-O-C7-acid is a versatile E3 ligase ligand-linker conjugate commonly used in the design and synthesis of PROTACs (Proteolysis Targeting Chimeras). By incorporating a thalidomide derivative with a tailored alkyl linker terminated with a carboxylic acid group, this compound is specifically optimized for efficient conjugation and targeted protein degradation approaches in biomedical research and drug discovery.

Mechanism

Thalidomide-O-C7-acid functions by recruiting the cereblon (CRBN) E3 ubiquitin ligase, a key component of the ubiquitin-proteasome system (UPS). The thalidomide moiety binds to CRBN, while the C7 alkyl linker with a terminal carboxylic acid enables facile coupling to ligands that target specific proteins of interest. When used as part of a PROTAC molecule, Thalidomide-O-C7-acid mediates formation of a ternary complex between the E3 ligase and the target protein. This proximity induces ubiquitination of the target protein, directing its subsequent degradation by the proteasome.

Applications

Thalidomide-O-C7-acid is widely applied in the synthesis of PROTACs, molecular glues, and other targeted protein degradation modalities. Its carboxylic acid functionality enhances the design flexibility for attaching various warheads or targeting ligands. Researchers employ this conjugate to develop chemical probes for protein function studies, identify therapeutic targets, and accelerate drug discovery programs across oncology, neurodegenerative diseases, and beyond. Its utility as a CRBN-engaging ligand-linker makes it a valuable building block for next-generation protein degradation technologies.