Jiang, Xueyang; Zhou, Junting; Wang, Yang; Liu, Xin; Xu, Kaiying; Xu, Jian; Feng, Feng; Sun, Haopeng published the artcile< PROTACs suppression of GSK-3β, a crucial kinase in neurodegenerative diseases>, Category: bromides-buliding-blocks, the main research area is neurodegenerative diseases proteolysis targeting chimera GSK 3beta protein degradation; Glycogen synthase kinase 3β; Neurodegenerative diseases; Proteolysis targeting chimera.
Glycogen synthase kinase 3β (GSK-3β) is involved in a variety of diseases such as neurodegenerative diseases, bipolar disorder, and diabetes. In this study, a series of heterobifunctional small mol. proteolysis targeting chimera (PROTAC) were designed and synthesized based on E3 ubiquitin ligase cereblon (CRBN). Most of PROTACs displayed good inhibitory activity, with the IC50 values at the double-digits nanomolar levels and moderate protein degradation ability against GSK-3β. Western-blot data showed compound PG21(I) can effectively degrade GSK-3β in a dose-dependent manner, which can induce 44.2% protein degradation at 2.8μM. Further pharmacol. experiments revealed that the ability of PG21 to degrade GSK-3β is mediated by the ubiquitin-proteasome system (UPS). In addition, PG21 protects against glutamate-induced cell death in HT-22 cells. As the first PROTAC example to degrade GSK-3β protein, the present study has provided potential candidates for further investigation in the biol. function of GSK-3β protein and its association with diseases.
European Journal of Medicinal Chemistry published new progress about Cereblons Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 337536-14-8 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8Br2O2, Category: bromides-buliding-blocks.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary