Inhibition of Protein Kinase C-Driven Nuclear Factor-κB Activation: Synthesis, Structure−Activity Relationship, and Pharmacological Profiling of Pathway Specific Benzimidazole Probe Molecul

详细信息    查看全文

• 作者：Satyamaheshwar Peddibhotla ; Ranxin Shi ; Pasha Khan ; Layton H. Smith ; Arianna Mangravita-Novo ; Michael Vicchiarelli ; Ying Su ; Karl J. Okolotowicz ; John R. Cashman ; John C. Reed ; Gregory P. Roth
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：June 24, 2010
• 年：2010
• 卷：53
• 期：12
• 页码：4793-4797
• 全文大小：798K
• 年卷期：v.53,no.12(June 24, 2010)
• ISSN：1520-4804

文摘

A unique series of biologically active chemical probes that selectively inhibit NF-κB activation induced by protein kinase C (PKC) pathway activators have been identified through a cell-based phenotypic reporter gene assay. These 2-aminobenzimidazoles represent initial chemical tools to be used in gaining further understanding on the cellular mechanisms driven by B and T cell antigen receptors. Starting from the founding member of this chemical series 1a (notated in PubChem as CID-2858522), we report the chemical synthesis, SAR studies, and pharmacological profiling of this pathway-selective inhibitor of NF-κB activation.