191732-76-0

Usage

Uses

Used in Pharmaceutical Industry:
5-amino-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione is used as a research compound for the development of novel protein degradation therapies. Its application in this field is due to its structural similarity to thalidomide, which allows it to be utilized in the design and synthesis of new PROTACs that can selectively target and degrade specific proteins involved in disease pathways.
Used in Research and Development:
In the context of research and development, 5-amino-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione serves as a valuable tool for scientists to study the mechanisms of protein degradation and to identify potential therapeutic targets for various diseases. Its use in this application is driven by the need to develop innovative and effective treatments that can address unmet medical needs.
Used in Drug Discovery:
5-amino-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione is also used in drug discovery efforts, where it can be employed to identify new lead compounds with potential therapeutic applications. Its use in this area is based on its ability to modulate protein degradation pathways, which can provide insights into the development of new drugs that can target specific proteins for degradation, thereby offering a new approach to treating diseases.

Upstream product

• 55003-81-1 2-(2,6-dioxo-3-piperidinyl)-5-nitro-1H-isoindole-1,3(2H)-dione 
• 2650-64-8 Cbz-L-Gln 
• 24666-56-6 rac-α-aminoglutarimide hydrochloride 
• 85535-45-1 5-amino-2-(tert-butoxycarbonylamino)-5-oxo-pentanoic acid 
• 31140-42-8 (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester 
• 24666-55-5 3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine 
• 5466-84-2 4-nitrophthalic anhydride 

Relevant academic research and scientific papers

Facile synthesis of an azido-labeled thalidomide analogue

(Matrix presented) A five-step synthesis of an azido-thalidomide analogue is presented. The sequence requires cheap and readily available starting materials and reagents, and only two steps require purification. Additionally, the azido-labeled analogue possesses activity comparable to that of thalidomide in inhibiting the proliferation of human microvascular endothelial cells, thus providing impetus for its use as a potential photoaffinity label of thalidomide.

Influence of Linker Attachment Points on the Stability and Neosubstrate Degradation of Cereblon Ligands

Proteolysis targeting chimeras (PROTACs) hijacking the cereblon (CRBN) E3 ubiquitin ligase have emerged as a novel paradigm in drug development. Herein we found that linker attachment points of CRBN ligands highly affect their aqueous stability and neosubstrate degradation features. This work provides a blueprint for the assembly of future heterodimeric CRBN-based degraders with tailored properties.

Compound for targeted degradation of adhesion spot kinase and application thereof (by machine translation)

The invention belongs to the technical field of medicines, and provides a compound as shown in general formula (I) and geometric isomers or pharmaceutically acceptable salts, hydrates, solvates, prodrugs and a preparation method thereof. The compound has good degradation activity on the adhesion spot kinase (FAK). The compounds, and geometric isomers or pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof are as shown in the general formula I, wherein Y, L, X, Z, R1 What is claimed is: the claims and the description. (by machine translation)

IMIDE-BASED MODULATORS OF PROTEOLYSIS AND METHODS OF USE

The description relates to imide-based compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

Efficient Synthesis of Immunomodulatory Drug Analogues Enables Exploration of Structure–Degradation Relationships

The immunomodulatory drugs (IMiDs) thalidomide, pomalidomide, and lenalidomide have been approved for the treatment of multiple myeloma for many years. Recently, their use as E3 ligase recruiting elements for small-molecule-induced protein degradation has led to a resurgence in interest in IMiD synthesis and functionalization. Traditional IMiD synthesis follows a stepwise route with multiple purification steps. Herein we describe a novel one-pot synthesis without purification that provides rapid access to a multitude of IMiD analogues. Binding studies with the IMiD target protein cereblon (CRBN) reveals a narrow structure–activity relationship with only a few compounds showing sub-micromolar binding affinity in the range of pomalidomide and lenalidomide. However, anti-proliferative activity as well as Aiolos degradation could be identified for two IMiD analogues. This study provides useful insight into the structure–degradation relationships for molecules of this type as well as a rapid and robust method for IMiD synthesis.

REGULATING CHIMERIC ANTIGEN RECEPTORS

This invention is in the area of compositions and methods for regulating chimeric antigen receptor immune effector cell, for example T-cell (CAR-T), therapy to modulate associated adverse inflammatory responses, for example, cytokine release syndrome and tumor lysis syndrome, using targeted protein degradation.

TUNABLE ENDOGENOUS PROTEIN DEGRADATION WITH HETEROBIFUNCTIONAL COMPOUNDS

The present invention provides a means to modulate gene expression in vivo in a manner that avoids problems associated with CRISPR endogenous protein knock-out or knock-in strategies and strategies that provide for correction, or alteration, of single nucleotides. The invention includes inserting into the genome a nucleotide encoding a heterobifunctional compound targeting protein (dTAG) in-frame with the nucleotide sequence of a gene encoding an endogenously expressed protein of interest which, upon expression, produces an endogenous protein-dTAG hybrid protein. This allows for targeted protein degradation of the dTAG and the fused endogenous protein using a heterobifunctional compound.

Methods and Compositions Using Immunomodulatory Compounds for the Treatment and Management of Spirochete and Other Obligate Intracellular Bacterial Diseases

Methods of treating, preventing and/or managing a spirochete and/or other obligate intracellular bacterial disease or disorder are disclosed. Specific methods encompass the administration of an immunomodulatory compound alone or in combination with a second active agent.

Preliminary biological evaluations of new thalidomide analogues for multiple sclerosis application

The present work deals with the synthesis of a new series of thalidomide derivatives for therapeutic applications. These compounds were evaluated in vitro on a human endothelial cell line EA.hy926 for their antiproliferative potential and in vivo on an experimental animal multiple sclerosis model called EAE as angiogenesis inhibitors. The preliminary results obtained on EAE assays seem to validate that anti-angiogenesis compounds could be promising tools for the treatment of MS.

IMMUNOTHERAPY FOR HEMATOLOGICAL MALIGNANCIES

Methods and compositions for treating, preventing and/or managing various hematological malignancies are disclosed. Specific methods and compositions relate to use of tumor cells engineered to express antigen presenting molecules which present antigens recognized by iNKT cells and eliciting antitumor immune response from iNKT cells using such tumor cells, optionally in combination with an immunomodulatory compound.