Name: Pomalidomide 4'-PEG2-azide
Brand: BOC Sciences
Rating: 5 (1 reviews)

Storage

Powder, -20°C, 3 years; 4°C, 2 years; In solvent, -80°C, 6 months; -20°C, 1 month

Shipping

Room temperature in continental US; may vary elsewhere.

IUPACName

4-[2-[2-(2-azidoethoxy)ethoxy]ethylamino]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione

InChI Key

BBYXCRBBKSBKOA-UHFFFAOYSA-N

InChI

1S/C19H22N6O6/c20-24-22-7-9-31-11-10-30-8-6-21-13-3-1-2-12-16(13)19(29)25(18(12)28)14-4-5-15(26)23-17(14)27/h1-3,14,21H,4-11H2,(H,23,26,27)

Canonical SMILES

[N-]=[N+]=NCCOCCOCCNC1=C2C(N(C(C2=CC=C1)=O)C3CCC(NC3=O)=O)=O

Pub Chem ID

137321407

Background Introduction

Pomalidomide 4'-PEG2-azide is a versatile bifunctional molecule designed for use in targeted protein degradation studies, particularly in the development of PROTACs (Proteolysis Targeting Chimeras). It features a pomalidomide moiety, which serves as a ligand for recruiting the cereblon (CRBN) E3 ubiquitin ligase, combined with a PEG2-azide linker that allows rapid and flexible conjugation to various target-binding ligands. This reagent is widely used by researchers exploring next-generation therapeutics for cancer, neurological disorders, and other diseases.

Mechanism

Pomalidomide 4'-PEG2-azide operates by exploiting the ubiquitin-proteasome system, the cell’s natural protein degradation pathway. The pomalidomide portion of the molecule selectively binds to the CRBN E3 ubiquitin ligase, one of the major E3 ligases leveraged in PROTAC design. The PEG2-azide linker enables click chemistry-based attachment to other molecular modules, such as target protein binders or fluorophores. When incorporated into a PROTAC, this conjugate bridges the target protein and CRBN, facilitating the ubiquitination and subsequent proteasomal degradation of the target protein.

Applications

Pomalidomide 4'-PEG2-azide is primarily used as a building block in PROTAC synthesis, accelerating the development of custom protein degraders for drug discovery. Its azide-functionalized linker is amenable to Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) or other click chemistry-based conjugations, streamlining the assembly of bifunctional molecules. Researchers utilize this product for generating a wide range of PROTACs aimed at degrading therapeutically relevant proteins, investigating cellular mechanisms, and validating new drug targets. Additionally, it serves as a valuable tool in chemical biology for labeling and tracking proteins in live-cell imaging and proximity labeling experiments.

• Azide-functionalized PEG2 linker enables versatile click chemistry conjugation for efficient PROTAC assembly.
• Specifically designed for CRBN E3 ligase recruitment, facilitating targeted protein degradation applications.

1. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial

Meletios A Dimopoulos, Evangelos Terpos, Mario Boccadoro, et al. Clinical TrialLancet Oncol. 2021 Jun;22(6):801-812.doi: 10.1016/S1470-2045(21)00128-5.

Background:In a phase 1b study, intravenous daratumumab plus pomalidomide and dexamethasone induced a very good partial response or better rate of 42% and was well tolerated in patients with heavily pretreated multiple myeloma. We aimed to evaluate whether daratumumab plus pomalidomide and dexamethasone would improve progression-free survival versus pomalidomide and dexamethasone alone in patients with previously treated multiple myeloma.

2. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study

Michel Attal, Paul G Richardson, S Vincent Rajkumar, et al. Clinical TrialLancet. 2019 Dec 7;394(10214):2096-2107.doi: 10.1016/S0140-6736(19)32556-5.Epub 2019 Nov 14.

Background:Isatuximab is a monoclonal antibody that binds a specific epitope on the human CD38 receptor and has antitumour activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of isatuximab with pomalidomide and low-dose dexamethasone. The aim of this study was to determine the progression-free survival benefit of isatuximab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma.

3. Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma

Meletios A Dimopoulos, Dominik Dytfeld, Sebastian Grosicki, Philippe Moreau, Naoki Takezako, Mitsuo Hori, Xavier Leleu, Richard LeBlanc, Kenshi Suzuki, Marc S Raab, Paul G Richardson, Mihaela Popa McKiver, Ying-Ming Jou, Suresh G Shelat, Michael Robbins, Brian Rafferty, Jesús San-Miguel Clinical TrialN Engl J Med. 2018 Nov 8;379(19):1811-1822.doi: 10.1056/NEJMoa1805762.

Background:The immunostimulatory monoclonal antibody elotuzumab plus lenalidomide and dexamethasone has been shown to be effective in patients with relapsed or refractory multiple myeloma. The immunomodulatory agent pomalidomide plus dexamethasone has been shown to be effective in patients with multiple myeloma that is refractory to lenalidomide and a proteasome inhibitor.

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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂