Thalidomide 4'-ether-alkylC2-amine hydrochloride

 CAS No.: 2341840-99-9  Cat No.: BP-100125  Purity: ≥95% by HPLC  HPLC  MS  HNMR 4.5  

Thalidomide 4'-ether-alkylC2-amine hydrochloride is a specialized E3 Ligase Ligand-Linker Conjugate designed for use in PROTAC (Proteolysis Targeting Chimera) drug development. This compound features a thalidomide-based E3 ligase recruiting motif linked via a two-carbon alkylamine linker, making it ideal for assembling bifunctional molecules that harness the ubiquitin-proteasome system. As a building block in the synthesis of PROTACs, Thalidomide 4'-ether-alkylC2-amine hydrochloride facilitates targeted protein degradation by selectively recruiting cereblon (CRBN) E3 ligase to the protein of interest. This product serves as a key intermediate for researchers working to design next-generation therapeutics aimed at previously 'undruggable' targets, offering routes to innovative treatments in oncology, neurology, and immunology. With its high purity and ready-to-use hydrochloride salt form, it ensures robust and reproducible PROTAC assembly for academic and pharmaceutical research.

Thalidomide 4'-ether-alkylC2-amine hydrochloride

Structure of 2341840-99-9

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Category
E3 Ligase Ligand-Linker Conjugate
Molecular Formula
C₁₅H₁₆ClN₃O₅
Molecular Weight
353.76

* For research and manufacturing use only. Not for human or clinical use.

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500 mg $1099 In stock

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Popular Publications Citing BOC Sciences Products
Purity
≥95% by HPLC
Storage
Store at -20°C
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Room temperature in continental US; may vary elsewhere.
IUPACName
4-(2-aminoethoxy)-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione;hydrochloride
Synonyms
Thalidomide - linker 6
InChI Key
AZQNUQDFOMUSBB-UHFFFAOYSA-N
InChI
1S/C15H15N3O5.ClH/c16-6-7-23-10-3-1-2-8-12(10)15(22)18(14(8)21)9-4-5-11(19)17-13(9)20;/h1-3,9H,4-7,16H2,(H,17,19,20);1H
Canonical SMILES
NCCOC1=C2C(N(C(C2=CC=C1)=O)C3CCC(NC3=O)=O)=O.Cl

Background Introduction

Thalidomide 4'-ether-alkylC2-amine hydrochloride is a synthetic small molecule designed as a versatile E3 ligase ligand-linker conjugate. It features a thalidomide core structure, renowned for its cereblon (CRBN) binding properties, linked via a 2-carbon (C2) alkyl chain terminated with an amine hydrochloride group. This optimized structure facilitates its integration into Proteolysis Targeting Chimeras (PROTACs) for targeted protein degradation strategies. As an advanced building block, this molecule enables streamlined assembly of functional PROTACs to selectively manipulate protein homeostasis within cells.

Mechanism

This compound operates by harnessing thalidomide’s ability to bind to the CRBN E3 ubiquitin ligase, a pivotal element in the ubiquitin-proteasome system. The 4'-ether-alkylC2-amine linker allows the thalidomide moiety to be chemically conjugated to a target protein ligand, forming a functional PROTAC molecule. Upon administration, the bifunctional PROTAC brings the protein of interest into close proximity with the CRBN E3 ligase, promoting polyubiquitination and subsequent proteasomal degradation of the target protein. This selective mechanism bypasses the need for traditional enzyme inhibition, offering a powerful route to modulate previously ‘undruggable’ proteins.

Applications

Thalidomide 4'-ether-alkylC2-amine hydrochloride is widely used in the development of next-generation PROTAC molecules and related targeted protein degradation technologies. Its primary applications include the synthesis of bespoke PROTACs for research in cellular biology, drug discovery, and identification of novel therapeutic targets. The compound serves as a modular E3 ligase recruiting handle, facilitating the creation of libraries of protein degraders aimed at oncology, neurodegenerative diseases, immunology, and beyond. As a result, it is a highly valuable tool for academic labs and pharmaceutical R&D focusing on innovative small molecule therapeutics.

• Amine-functionalized linker enables efficient coupling in PROTAC assembly
• Designed to support selective CRBN E3 ligase recruitment for targeted protein degradation applications
1. Mantle Cell Lymphoma
John F Seymour, Michael L Wang, Chan Yoon Cheah J Clin Oncol . 2016 Apr 10;34(11):1256-69. doi: 10.1200/JCO.2015.63.5904.
Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma previously considered to have a poor prognosis. Large gains were made in the first decade of the new century when clinical trials established the importance of high-dose therapy and autologous stem-cell rescue and high-dose cytarabine in younger patients and the benefits of maintenance rituximab and bendamustine in older patients. In particular, greater depth of understanding of the molecular pathophysiology of MCL has resulted in an explosion of specifically targeted new efficacious agents. In particular, agents recently approved by the Food and Drug Administration include the proteasome inhibitor bortezomib, immunomodulator lenalidomide, and Bruton's tyrosine kinase inhibitor ibrutinib. We review recent advances in the understanding of MCL biology and outline our recommended approach to therapy, including choice of chemoimmunotherapy, the role of stem-cell transplantation, and mechanism-based targeted therapies, on the basis of a synthesis of the data from published clinical trials.
2. Bendamustine in multiple myeloma
Ernesto Vigna, Massimo Gentile, Francesco Mendicino, Anna Grazia Recchia, Lucio Morabito, Giovanna Giagnuolo, Fortunato Morabito Eur J Haematol . 2015 Nov;95(5):377-88. doi: 10.1111/ejh.12609.
The advent of high-dose melphalan with autologous stem-cell transplantation (ASCT), the availability of novel agents such as thalidomide, lenalidomide (immunomodulatory drugs or IMiDs) and bortezomib (proteasome inhibitor) and improvements in supportive care have allowed to increase overall survival in multiple myeloma (MM) patients; nevertheless, MM remains an incurable pathology. For this reason, newer agents are required for continued disease control. Bendamustine is an old drug rediscovered in the last decade. In fact, its unique mechanism of action with structural similarities to both alkylating agents and antimetabolities, but which is not cross-resistant to alkylating agents, has reawakened interest in the use of this drug in the treatment of MM. Studies have proven the safety and efficacy of bendamustine administered alone or in combination with new drugs in both upfront and relapse/refractory settings of MM patients, including those with renal impairment. Moreover, bendamustine has been successfully used as conditioning for autologous stem-cell transplantation. Finally, the use of bendamustine does not compromise peripheral blood stem-cell collection. This drug is generally well tolerated, with the majority of adverse events being due to myelosuppression. Non-haematological adverse events are infrequent and usually mild.
3. Pharmacology of oral chemotherapy agents
Ann Birner Clin J Oncol Nurs . 2003 Nov-Dec;7(6 Suppl):11-9. doi: 10.1188/03.CJON.S6.11-19.
The abundance of orally formulated chemotherapy agents reflects the expanding role of oral chemotherapy in the care of patients with cancer. Many oral chemotherapy agents have been used for a number of years, and several have been developed recently. Newer agents include the prodrugs capecitabine and temozolomide, the retinoid bexarotene, the immunomodulatory agent thalidomide, the protein kinase inhibitor imatinib, and the epidermal growth factor receptor inhibitors gefitinib and erlotinib. Each agent has unique pharmacologic properties, dosing, and side-effect profiles. This article reviews these agents from a pharmacology perspective.

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It is commonly abbreviated as: C1V1 = C2V2

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