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Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents

Editor-in-Chief

ISSN (Print): 1568-0142
ISSN (Online): 1875-6131

Identification of a Novel Inhibitor of the NF-κB Pathway

Author(s): A. Misra-press, M. McMillan, E. Cudaback, M. Qabar, F. Ruan, M. Nguyen, T. Vaisar, H. Nakanishi and M. Kahn

Volume 1, Issue 1, 2002

Page: [29 - 39] Pages: 11

DOI: 10.2174/1568014024606566

Abstract

NF-κB1 plays a central role in regulating genes involved in inflammatory responses, and its recently described role in oncogenesis reemphasizes its importance as a critical mediator of cellular function. We describe herein a novel inhibitor (MOL-294) of NF-κB driven transcription that does not inhibit the proteasome complex, does not inhibit IκB2 phosphorylation, and does not significantly inhibit nuclear translocation of the p65 / RelA subunit of NF-κB. We have identified thioredoxin, a cellular redox protein, which has previously been implicated in the regulation of NF-κB driven transcription, as one of the intracellular targets of MOL-294. The identification of a low molecular weight inhibitor of this type of redox protein represents a novel mechanism of inhibiting the NF-κB signaling pathway.

Keywords: inhibitor, cytotoxicity


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