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Direct Rel/NF-κB inhibitors: structural basis for mechanism of action.
- Source :
-
Future medicinal chemistry [Future Med Chem] 2009 Dec; Vol. 1 (9), pp. 1683-707. - Publication Year :
- 2009
-
Abstract
- The Rel/NF-κB transcription factors have emerged as novel therapeutic targets for a variety of human diseases and pathological conditions, including inflammation, autoimmune diseases, cancer, ischemic injury, osteoporosis, transplant rejection and neurodegeneration. Several US FDA-approved drugs may, in part, attribute their therapeutic effects to the inhibition of the Rel/NF-κB pathway. Strategies for blocking the Rel/NF-κB signaling pathway have inspired the pharmaceutical industry to develop inhibitors for I-κB kinase, however, this article focuses instead on identifying natural compounds that directly target and inhibit DNA binding and transcription activity of Rel/NF-κB. These include compounds containing a quinone core, an α,β unsaturated carbonyl and a benzene diamine. By investigating the mechanisms of action of existing natural inhibitors, novel strategies and synthetic approaches can be devised that will facilitate the development of novel and selective Rel/NF-κB inhibitors with better safety profiles.
- Subjects :
- Animals
Autoimmune Diseases drug therapy
Humans
I-kappa B Kinase antagonists & inhibitors
I-kappa B Kinase metabolism
Ketones chemistry
Ketones therapeutic use
Mice
NF-kappa B genetics
NF-kappa B metabolism
Neoplasms drug therapy
Neoplasms metabolism
Quinones chemistry
Quinones therapeutic use
Signal Transduction
Transcription Factor RelA genetics
Transcription Factor RelA metabolism
NF-kappa B antagonists & inhibitors
Transcription Factor RelA antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1756-8927
- Volume :
- 1
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Future medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 21425986
- Full Text :
- https://doi.org/10.4155/fmc.09.96