Pomalidomide-dipiperazine-NH2 hydrochloride

Background Introduction

Pomalidomide-dipiperazine-NH2 hydrochloride is an advanced E3 ligase ligand-linker conjugate designed for targeted protein degradation applications, particularly in Proteolysis Targeting Chimeras (PROTACs). Building on the structure of pomalidomide, a well-known immunomodulatory agent and cereblon (CRBN) E3 ligase recruiter, this product integrates a dipiperazine linker with an amino functionality, providing a versatile platform for the rational design of efficient PROTAC molecules.

Mechanism

The mechanism of Pomalidomide-dipiperazine-NH2 hydrochloride centers on its ability to engage the cereblon (CRBN) E3 ubiquitin ligase complex via the pomalidomide moiety. The dipiperazine linker functions as a flexible and hydrophilic spacer, optimizing the spatial orientation between the E3 ligase and a target protein ligand when forming a bifunctional PROTAC. The terminal amine group enables straightforward conjugation to various target-binding molecules. Upon successful recruitment of both CRBN and the protein of interest, the resulting ternary complex facilitates the ubiquitination and subsequent proteasomal degradation of the target protein, offering selective and catalytic protein knockdown.

Applications

Pomalidomide-dipiperazine-NH2 hydrochloride is widely utilized in medicinal chemistry and early-stage drug discovery for the modular assembly of PROTACs and related heterobifunctional degraders. Its superior physicochemical properties make it ideal for synthesizing PROTAC molecules targeting disease-relevant proteins in oncology, neurology, and immunology. Academic and pharmaceutical researchers employ this reagent to probe protein function, validate new therapeutic targets, and accelerate the development of next-generation targeted protein degradation therapies. The availability of a hydrochloride salt form enhances its solubility and stability, facilitating efficient chemical synthesis and biological characterization in laboratory settings.