Solubility

DMSO: ≥ 30 mg/mL (66.74 mM)

Appearance

Solid

Storage

Store at -20°C

Synonyms

(3S)-3-[7-[[4-(morpholin-4-ylmethyl)phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione; CC-220; CC220; CC 220; Iberdomide.

Boiling Point

717.8±60.0 °C at 760 Torr

Density

1.332±0.06 g/cm3

InChI Key

IXZOHGPZAQLIBH-NRFANRHFSA-N

InChI

1S/C25H27N3O5/c29-23-9-8-21(24(30)26-23)28-15-20-19(25(28)31)2-1-3-22(20)33-16-18-6-4-17(5-7-18)14-27-10-12-32-13-11-27/h1-7,21H,8-16H2,(H,26,29,30)/t21-/m0/s1

Canonical SMILES

C1CC(=O)NC(=O)C1N2CC3=C(C2=O)C=CC=C3OCC4=CC=C(C=C4)CN5CCOCC5

Background Introduction

Iberdomide (also known as CC-220) is a next-generation immunomodulatory imide drug (IMiD) structurally related to thalidomide, lenalidomide, and pomalidomide. As a potent ligand for the Cereblon (CRBN) E3 ubiquitin ligase, iberdomide exhibits enhanced binding affinity and favorable pharmacological properties compared to earlier IMiDs. It has garnered attention for its role in targeted protein degradation (TPD) strategies, particularly in the design and construction of PROTACs (Proteolysis Targeting Chimeras) and molecular glue degraders.

Mechanism

Iberdomide functions by binding to the CRBN protein, a substrate receptor within the CUL4-CRBN E3 ubiquitin ligase complex. This interaction facilitates the recruitment of the target protein to the E3 ligase, leading to polyubiquitination and subsequent proteasomal degradation of the target. Iberdomide's enhanced binding efficiency enables robust and selective degradation of disease-relevant proteins, such as transcription factors Ikaros (IKZF1) and Aiolos (IKZF3), making it an attractive component for diverse targeted degradation applications.

Applications

Iberdomide is widely used as a ligand in the development and optimization of CRBN-based PROTACs and molecular glue degraders. Its strong binding and selectivity contribute to efficient targeted protein degradation, supporting:

• Design and synthesis of next-generation PROTACs for therapeutic and biological research
• Discovery of novel molecular glue degraders that exploit CRBN for selective protein knockdown
• Exploration of new drug candidates for hematological malignancies and autoimmune diseases
• Medicinal chemistry campaigns aimed at improving the efficacy and specificity of E3 ligase-based degraders
• Custom synthesis for CROs, pharmaceutical R&D, and academic target validation research projects.

By leveraging iberdomide as a CRBN ligand, researchers can accelerate drug discovery and develop innovative therapies via targeted protein degradation.

• 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 binding to CRBN E3 ligase enhances targeted protein degradation efficiency.
• Demonstrates improved potency and reduced off-target toxicity for next-generation PROTAC design.

1.Antigenic differentiation of avian pneumovirus isolates using polyclonal antisera and mouse monoclonal antibodies.

Collins MS;Gough RE;Alexander DJ Avian Pathol. 1993 Sep;22(3):469-79.

Avian pneumovirus (AVP) isolates F83, CC220 and 1260 from Great Britain and 1556, 657/4, 2119 and 872/S from France, Hungary, Italy and Spain, respectively, were compared in ELISA and virus neutralization (VN) tests for reactions with chicken polyclonal sera against each of the viruses and monoclonal antibodies (MAbs) against two British isolates. ELISA test results using the polyclonal antisera indicated that all seven viruses were antigenically related, but some variation between strains could be detected, especially when antigens were prepared from infected cells using Nonidet P40 (NP40) rather than freezing and thawing. In VN tests results also showed that all viruses tested were related but there was evidence that the three British isolates showed closer relationships with each other than with the viruses from Italy, Hungary and Spain. In ELISA tests, isolates F83 and 1556 bound all 11 MAbs and 1260 reacted with 10/11 MAbs. Isolate CC220 showed reaction with all the MAbs but for 8/11 MAbs the optical density differences were low. Isolates 2119 and 872/S both reacted only with MAb 4 and none of the MAbs reacted with 657/4.

2.A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos.

Matyskiela ME;Zhang W;Man HW;Muller G;Khambatta G;Baculi F;Hickman M;LeBrun L;Pagarigan B;Carmel G;Lu CC;Lu G;Riley M;Satoh Y;Schafer P;Daniel TO;Carmichael J;Cathers BE;Chamberlain PP J Med Chem. 2018 Jan 25;61(2):535-542. doi: 10.1021/acs.jmedchem.6b01921. Epub 2017 Apr 20.

The drugs lenalidomide and pomalidomide bind to the protein cereblon, directing the CRL4-CRBN E3 ligase toward the transcription factors Ikaros and Aiolos to cause their ubiquitination and degradation. Here we describe CC-220 (compound 6), a cereblon modulator in clinical development for systemic lupus erythematosis and relapsed/refractory multiple myeloma. Compound 6 binds cereblon with a higher affinity than lenalidomide or pomalidomide. Consistent with this, the cellular degradation of Ikaros and Aiolos is more potent and the extent of substrate depletion is greater. The crystal structure of cereblon in complex with DDB1 and compound 6 reveals that the increase in potency correlates with increased contacts between compound 6 and cereblon away from the modeled binding site for Ikaros/Aiolos. These results describe a new cereblon modulator which achieves greater substrate degradation via tighter binding to the cereblon E3 ligase and provides an example of the effect of E3 ligase binding affinity with relevance to other drug discovery efforts in targeted protein degradation.

3.Recent topics in IMiDs and cereblon.

Ito T;Handa H Rinsho Ketsueki. 2017;58(10):2067-2073. doi: 10.11406/rinketsu.58.2067.

Immunomodulatory drugs (IMiDs) are a new class of anticancer compounds that are derived from thalidomide. Lenalidomide and pomalidomide are well-known IMiDs, and they have already been approved by FDA for the treatment of several diseases, including multiple myeloma. Cereblon (CRBN) is a common primary target for IMiDs. It works as a substrate receptor of CRL4. Accumulating evidence has shown that the substrate specificity of CRL4;CRBN; is altered by ligands such as IMiDs. Recently, novel CRBN-binding compounds have been developed and are called "cereblon modulators". Among these, CC-122 and CC-220 are currently under clinical development for the treatment of diffuse large B-cell lymphoma and systemic lupus erythematosus, respectively. Another new cereblon modulator CC-885 is shown to induce degradation of the translation termination factor GSPT1, resulting in an antiproliferative effect in acute myeloid leukemia. Structural analyses have revealed that CC-885 provides an interaction hotspot between CRBN and GSPT1. On the other hand, several groups have been investigating linker-based approaches for targeted protein degradation via CRBN. Several proteins, such as BRD4 and BCR-ABL, have been successfully degraded by CRL4;CRBN; using these technologies.

ConcentrationVolumeMass	1 mg	5 mg	10 mg
1 mM	2.2247 mL	11.1235 mL	22.2469 mL
5 mM	0.4449 mL	2.2247 mL	4.4494 mL
10 mM	0.2225 mL	1.1123 mL	2.2247 mL
50 mM	0.0445 mL	0.2225 mL	0.4449 mL

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* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂