Thalidomide-O-C4-NH2 hydrochloride

Background Introduction

Thalidomide-O-C4-NH2 hydrochloride is an innovative E3 ligase ligand-linker conjugate widely used as a building block in the synthesis of PROTACs (Proteolysis Targeting Chimeras). Derived from thalidomide, a well-known immunomodulatory drug, this compound features a functionalized linker designed for efficient conjugation with various target protein ligands. Its unique chemistry makes it an essential component for researchers focused on targeted protein degradation with enhanced selectivity and efficacy.

Mechanism

Thalidomide-O-C4-NH2 hydrochloride operates as an E3 ligase recruiter in the PROTAC construct. Specifically, the thalidomide moiety binds to Cereblon (CRBN), a substrate receptor of the Cullin-RING E3 ubiquitin ligase complex. The O-C4-NH2 linker allows flexible attachment of the CRBN-binding moiety to a target protein ligand. Once the PROTAC is assembled, it brings the target protein into close proximity with the E3 ligase, facilitating ubiquitination and subsequent proteasomal degradation of the target protein. This mechanism enables selective and efficient protein knockdown within cells.

Applications

Thalidomide-O-C4-NH2 hydrochloride is ideal for the development and optimization of PROTACs targeting disease-related proteins in cancer biology, neurodegenerative diseases, and autoimmune disorders. It serves as a critical intermediate in medicinal chemistry for designing next-generation protein degraders. This conjugate is also utilized in academic and pharmaceutical research to explore new target validation strategies, mechanism-of-action studies, and drug discovery programs emphasizing protein homeostasis and degradation pathways.

• Amine-functionalized linker enables easy and efficient conjugation to target ligands or payloads, streamlining PROTAC development.
• High affinity for the cereblon (CRBN) E3 ligase ensures reliable and robust degradation activity in PROTAC applications.