IkappaB kinase inhibitors for treating autoimmune and inflammatory disorders: potential and challenges.
The nuclear transcription factor NF-kappaB has a crucial role in the pathogenesis of several human disorders, particularly those with an inflammatory component. Because the multisubunit IkappaB kinase (IKK) is vital for translating pro-inflammatory stimuli into the activation of NF-kappaB, this kinase provides an opportunity to develop novel therapeutics. In this article, we review the investigations, both genetic and pharmacological, that demonstrate the use of IKK inhibition in autoimmune and inflammatory disorders. It is still unclear what toxicities will be associated with IKK inhibitors; a discussion of the potential for mechanism-based toxicities such as teratogenicity, lymphopoietic defects and susceptibility to infection is also presented.
Strnad
Joann
J
Immunology and Inflammation Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA.
Burke
James R
JR
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D004358:Drug Therapy / Q000379:methods / Q000639:trends; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D018448:Models, Immunological; D015394:Molecular Structure
D004791:Enzyme Inhibitors; D051550:I-kappa B Kinase