Naturally occurring and synthetic inhibitors of NF-kappaB functions.
Nuclear factor (NF)-kappaB is a transcription factor that induces the immunoglobulin kappa chain, cytokines such as interleukin (IL)-1, IL-2, IL-6, IL-8, tumor necrosis factor (TNF)-alpha and interferon gamma, and cell adhesion proteins. It also induces anti-apoptotic proteins, and inhibits TNF-alpha and anticancer drug-induced apoptosis. Therefore, NF-kappaB function inhibitors may be useful as anti-inflammatory and anticancer agents. Microbial products such as panepoxydone, cycloepoxydon and gliotoxin are known to inhibit activation of NF-kappaB. We have designed and synthesized new NF-kappaB inhibitors from the structure of an antibiotic, epoxyquinomicin C. The designed compound, DHM2EQ, inhibited TNF-alpha-induced activation of NF-kappaB and showed a therapeutic effect in mouse rheumatoid arthritis model.
Umezawa
K
K
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan. umezawa@applc.keio.ac.jp
Ariga
A
A
Matsumoto
N
N
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000302:isolation & purification / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D016328:NF-kappa B