原创力文档the anti-inflammatory drug leflunomide is an agonist of the aryl hydrocarbon receptor抗炎药物leflunomide芳基碳氢化合物受体的激动剂.pdfVIP
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the anti-inflammatory drug leflunomide is an agonist of the aryl hydrocarbon receptor抗炎药物leflunomide芳基碳氢化合物受体的激动剂
The Anti-Inflammatory Drug Leflunomide Is an Agonist
of the Aryl Hydrocarbon Receptor
1,2 2 1,2 1,2 2
Edmond F. O’Donnell , Katerine S. Saili , Daniel C. Koch , Prasad R. Kopparapu , David Farrer ,
1,2,3 2 2 2 2
William H. Bisson , Lijoy K. Mathew , Sumitra Sengupta , Nancy I. Kerkvliet , Robert L. Tanguay , Siva
Kumar Kolluri1,2*
1 Cancer Research Laboratory, Environmental Health Sciences Center, Oregon State University, Corvallis, Oregon, United States of America, 2 Department of
Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, Oregon, United States of America, 3 Pharmaceutical
Biochemistry Group, School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland
Abstract
Background: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and
biological activity of dioxins and related chemicals. The AhR influences a variety of processes involved in cellular growth and
differentiation, and recent studies have suggested that the AhR is a potential target for immune-mediated diseases.
Methodology/Principal Findings: During a screen for molecules that activate the AhR, leflunomide, an immunomodulatory
drug presently used in the clinic for the treatment of rheumatoid arthritis, was identified as an AhR agonist. We aimed to
determine whether any biological activity of leflunomide could be attributed to a previously unappreciated interaction with
the AhR. The currently established mechanism of action of leflunomide involves its me
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