Selective benzimidazole inhibitors of the antigen receptor-mediated NF-kappaB activation pathway.
Dysregulated antigen receptor-mediated NF-kappaB activation can contribute to development of autoimmunity, chronic inflammation, and malignancy. A chemical biology screening strategy has identified a substituted benzimidazole that selectively inhibits antigen receptor-mediated NF-kappaB activation without blocking other NF-kappaB activation pathways. A library of analogs was synthesized and the structure-activity relationship and metabolic stability for the series is presented.
Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA. kokolotowicz@hbri.org
Karl J
KJ
Okolotowicz
Ranxin
R
Shi
Xueying
X
Zheng
Mary
M
MacDonald
John C
JC
Reed
John R
JR
Cashman
D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011946:Receptors, Antigen / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
D001562:Benzimidazoles; D016328:NF-kappa B; D011946:Receptors, Antigen