2093536-12-8

Basic information

• Product Name: 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione
• CAS NO: 2093536-12-8
• Molecular Weight: 337.129
• Mol File: 2093536-12-8.mol
• Article Data: 16

Chemical Properties

• CAS DataBase Reference: 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione(CAS DataBase Reference)
• NIST Chemistry Reference: 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione(2093536-12-8)
• EPA Substance Registry System: 4-bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione(2093536-12-8)

Safety Data

• Hazardous Substances Data: 2093536-12-8(Hazardous Substances Data)

Usage

Description

4-Bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione is a thalidomide analog that can be useful in PROTAC research.

Upstream product

• 576-23-8 2,3-dimethylbromobenzene 
• 76006-33-2 3-bromo-2-methylbenzoic acid 
• 82-73-5 3-bromophthalic anhydride 
• 2686-86-4 3-aminopiperidine-2,6-dione hydrochloric acid salt 
• 2353-44-8 (+/-)-α-aminoglutarimide 
• 116-69-8 3-bromophthalic acid 
• 24666-56-6 rac-α-aminoglutarimide hydrochloride 
• 99548-54-6 methyl 3-bromo-2-methylbenzoate 

Downstream Products

• 19171-19-8 pomalidomide 

Relevant articles and documents

Discovery of novel BCR-ABL PROTACs based on the cereblon E3 ligase design, synthesis, and biological evaluation

Protein degradation is a promising strategy for drug development. Proteolysis-targeting chimeras (PROTACs) hijacking the E3 ligase cereblon (CRBN) exhibit enormous potential and universal degradation performance due to the small molecular weight of CRBN ligands. In this study, the CRBN-recruiting PROTACs were explored on the degradation of oncogenic fusion protein BCR-ABL, which drives the pathogenesis of chronic myeloid leukemia (CML). A series of novel PROTACs were synthesized by conjugating BCR-ABL inhibitor dasatinib to the CRBN ligand including pomalidomide and lenalidomide, and the extensive structure-activity relationship (SAR) studies were performed focusing on optimization of linker parameters. Therein, we uncovered that pomalidomide-based degrader 17 (SIAIS056), possessing sulfur-substituted carbon chain linker, exhibits the most potent degradative activity in vitro and favorable pharmacokinetics in vivo. Besides, degrader 17 also degrades a variety of clinically relevant resistance-conferring mutations of BCR-ABL. Furthermore, degrader 17 induces significant tumor regression against K562 xenograft tumors. Our study indicates that 17 as an efficacious BCR-ABL degrader warrants intensive investigation for the future treatment of BCR-ABL+ leukemia.

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.

HETEROCYCLIC DERIVATIVES

Compounds of the formula (I): Q1-Q2-Q3, in which Q1, Q2 and Q3 have the meanings indicated in Claim 1, degrade target proteins, and can be employed, inter alia, for the treatment of diseases such as cancer, multiple sclerosis, cardiovascular diseases, central nervous system injury and different forms of inflammation.