Researchers at The Pennsylvania State University College of Medicine, Hershey, Pennsylvania have discovered that the efficacy of imiquimod, a clinically important immune response modifier with potent antiviral and antitumor activity, is dependent on the Opioid Growth Factor (OGF)-OGF receptor (OGFr) axis for its action. This discovery, reported in the August 08 issue of Experimental Biology and Medicine, provides new insights into a widely used drug that may lead to development of new agents that will enhance effectiveness and attenuate side-effects.
Imiquimod and resiquimod are imidazoquinoline compounds. Imiquimod (Aldara, R-837, S26308), the best characterized and most widely used, is highly efficacious in the treatment of external genital and anal warts, basal cell carcinoma, actinic keratoses, Kaposi's sarcoma, chronic hepatitis C infection, and intraepithelial carcinoma. Therefore, the underlying mechanism of imiquimod action is of clinical importance. Imiquimod has been reported to be a toll-like receptor-7 agonist, and its anti-tumor effect exerted by modification of the immune response and stimulation of apoptosis. The mechanism of imiquimod on cell proliferation is unclear.
The research team, led by Dr. Ian S. Zagon, Distinguished University Professor, and Dr. Patricia J. McLaughlin, Professor, along with a pre-doctoral student Renee N. Donahue, in the Department of Neural & Behavioral Sciences and collaborator Moshe Rogosnitzky of MedInsight explored mechanisms responsible for the remarkable clinical action of this class of drugs. Specifically, using tissue culture models, the investigators found that imidazoquinolines upregulate OGFr which in turn stimulates the interaction of the OGF-OGFr axis. This native, tonically active inhibitory pathway is known to regulate cell proliferation by modulating cyclin dependent kinase inhibitors, resulting in a retardation of cells at the G1-S interface of the cell cycle. Neutraliz
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Society for Experimental Biology and Medicine