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Inhibition of protein kinase C-driven nuclear factor-kappaB activation: synthesis, structure-activity relationship, and pharmacological profiling of pathway specific benzimidazole probe molecules.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2010 Jun 24; Vol. 53 (12), pp. 4793-7. - Publication Year :
- 2010
-
Abstract
- A unique series of biologically active chemical probes that selectively inhibit NF-kappaB 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-kappaB activation.
- Subjects :
- Animals
Benzimidazoles pharmacokinetics
Benzimidazoles pharmacology
Cell Line
Cell Membrane Permeability
Genes, Reporter
Hepatocytes cytology
Hepatocytes drug effects
Humans
Hydrophobic and Hydrophilic Interactions
Interleukin-2 biosynthesis
Interleukin-8 biosynthesis
Male
Mice
Microsomes, Liver metabolism
NF-kappa B genetics
NF-kappa B physiology
Receptors, Antigen, B-Cell physiology
Receptors, Antigen, T-Cell physiology
Signal Transduction
Small Molecule Libraries
Structure-Activity Relationship
Benzimidazoles chemical synthesis
NF-kappa B antagonists & inhibitors
Protein Kinase C physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 53
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 20481485
- Full Text :
- https://doi.org/10.1021/jm1000248