3-(1-oxo-3,5,6,7-tetrahydropyrrolo[3,4-f]isoindol-2-yl)piperidine-2,6-dione

Background Introduction

3-(1-oxo-3,5,6,7-tetrahydropyrrolo[3,4-f]isoindol-2-yl)piperidine-2,6-dione is a potent Cereblon (CRBN) E3 ligase ligand belonging to the class of immunomodulatory imide drug (IMiD) analogs. As a key structural motif derived from thalidomide-based frameworks, this compound incorporates optimized features for stable and high-affinity binding to the CRBN E3 ubiquitin ligase complex. Its design facilitates reliable integration into PROTAC (Proteolysis Targeting Chimera) molecules and targeted protein degradation strategies.

Mechanism

This compound functions as a small-molecule ligand specifically binding to the CRBN substrate recognition site within the CRBN-DDB1-CUL4A-RBX1 E3 ubiquitin ligase complex. By serving as a molecular bridge in PROTAC constructs, it promotes the recruitment of CRBN ligase to the protein-of-interest, leading to polyubiquitination and subsequent proteasomal degradation. This mechanism enables selective and efficient depletion of target proteins by harnessing the body's endogenous protein degradation machinery.

Applications

3-(1-oxo-3,5,6,7-tetrahydropyrrolo[3,4-f]isoindol-2-yl)piperidine-2,6-dione is extensively utilized in the construction of rationally designed CRBN-recruiting PROTACs for targeted protein degradation. It serves as a versatile chemical handle for linking E3 ligase recruiting motifs to target protein ligands through a variety of linker strategies. Primary applications include:

• Synthesis of next-generation PROTACs and molecular glue degraders using CRBN-based ligands
• Drug discovery programs targeting previously undruggable proteins
• Target validation, mechanism-of-action studies, and SAR (Structure-Activity Relationship) optimization
• Development of chemical biology probes and tool compounds for academic and pharmaceutical research

By leveraging this ligand, researchers can accelerate the discovery of novel targeted therapies and expand the toolbox for chemical biology and therapeutic target engagement.

• High-purity compound verified by HPLC, NMR, and LC-MS
• Consistent batch-to-batch reproducibility with complete QC documentation
• Supplied with COA, MSDS, and analytical data for traceability
• Reliable global shipping with stability-guaranteed packaging
• Dedicated technical support and optional custom synthesis service
• Demonstrates strong binding affinity to CRBN, VHL, or other E3 ligases
• Enables stable E3 ligase recruitment for targeted protein degradation
• Selective cereblon (CRBN) ligand for efficient E3 ligase recruitment in PROTAC development.
• Enables design of highly potent targeted protein degraders for challenging therapeutic targets.