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Immunosuppressant discovery from Tripterygium wilfordii(5R)-5-hydroxytriptolide (LLDT-8).pdf

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Immunosuppressant discovery from Tripterygium wilfordii(5R)-5-hydroxytriptolide (LLDT-8)

Acta Pharmacologica Sinica (2012) 33: 1112–1118 ? 2012 CPS and SIMM All rights reserved 1671-4083/12 $32.00 /aps npg Immunosuppressant discovery from Tripterygium wilfordii Hook f: the novel triptolide analog (5R)-5- hydroxytriptolide (LLDT-8) Wei TANG, Jian-ping ZUO* Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China The Chinese traditional herb Tripterygium wilfordii Hook f (TwHF) has been widely used in the treatment of autoimmune and inflammatory diseases. Over the past few decades, great efforts have been made to explore modern preparations of TwHF with higher efficacy, solubility, and lower toxicity. In this study, we reviewed several examples both of naturally occurring compounds and their derivatives in TwHF, and summarized the preclinical evaluations with regard to autoimmune and inflammatory diseases. All of the candidate compounds described herein have been or are currently in clinical trials. Although some studies encountered problems, the data still provided valuable references for future studies. (5R)-5-hydroxytriptolide (LLDT-8, Leitengshu) is a novel triptolide derivative with potent immunosuppressive and anti-inflammatory activities developed at Shanghai Institute of Materia Medica. Indeed, a Phase I clinical trial for this compound has been completed in rheumatoid arthritis patients. The results will provide the basis for the further exploration of this ancient herb and encourage the research and development of valuable traditional Chinese medicine. Keywords: Tripterygium wilfordii Hook f; triptolide; (5R)-5-hydroxytriptolide (LLDT-8); autoimmune diseases; immunosuppressants; clini- cal trials Acta Pharmacologica Sinica (2012) 33: 1112–1118; doi: 10.1038/aps.2012.108; published online 27 Aug 2012 Introduction For thousands of years, natural products have played an important role throughout the world in treating