Thalidomide-NH-C5-NH2 hydrochloride

Background Introduction

Thalidomide-NH-C5-NH2 hydrochloride is an advanced E3 ligase ligand-linker conjugate used as a key building block in the synthesis of PROTACs (Proteolysis Targeting Chimeras). This compound features a thalidomide-based cereblon (CRBN) E3 ligase ligand, linked via a flexible C5 linker terminating with a primary amine (NH2) group. This design enables efficient coupling with target-binding warheads, making it essential for researchers developing innovative targeted protein degradation therapies.

Mechanism

Thalidomide-NH-C5-NH2 hydrochloride exerts its function as part of a PROTAC molecule. The thalidomide moiety binds selectively to the cereblon (CRBN) E3 ubiquitin ligase, recruiting it to specific target proteins. Through its C5 linker with terminal amine, this ligand can be conjugated to various target ligands or warheads, forming bifunctional molecules. These chimeric compounds induce proximity between the E3 ligase and the protein of interest (POI), resulting in polyubiquitination and subsequent proteasome-mediated degradation of the target protein.

Applications

Thalidomide-NH-C5-NH2 hydrochloride is primarily applied in the synthesis of custom PROTAC molecules for targeted ubiquitination and degradation studies. Its amine-functionalized linker allows for versatile conjugation chemistry (e.g., amide bond formation) with diverse protein-targeting ligands, enabling the creation of PROTAC libraries aimed at a wide variety of disease-associated proteins. This material is widely used in drug discovery research, cellular target validation, and preclinical therapeutic development targeting cancers, neurodegenerative diseases, and other conditions driven by pathogenic proteins.

• Amine-terminated C5 linker ensures flexible and stable attachment for diverse warhead conjugation.
• Specifically designed for efficient synthesis of CRBN-recruiting PROTACs, improving targeted protein degradation.