nsaids old drugs reveal new anticancer targets非甾体抗炎药老新抗癌药物揭示目标.pdfVIP

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nsaids old drugs reveal new anticancer targets非甾体抗炎药老新抗癌药物揭示目标.pdf

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nsaids old drugs reveal new anticancer targets非甾体抗炎药老新抗癌药物揭示目标

Pharmaceuticals 2010, 3, 1652-1667; doi:10.3390/ph3051652 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review NSAIDs: Old Drugs Reveal New Anticancer Targets Gary A. Piazza 1,2,*, Adam B. Keeton 1 , Heather N. Tinsley 2, Jason D. Whitt 2, Bernard D. Gary 1, Bini Mathew 1, Raj Singh 3, William E. Grizzle 2 and Robert C. Reynolds 1,2 1 Southern Research Institute, 2000 9th Avenue South, Birmingham AL, 35205, USA 2 The University of Alabama at Birmingham, 703 19th Street South, Birmingham AL, 35294, USA 3 Vivo Biosciences Inc., 1601 12th Avenue South, Birmingham AL, 35205, USA * Author to whom correspondence should be addressed; E-Mail: piazza@; Tel. +1-205-581-2731; Fax: +1-205-581-2093. Received: 16 March 2010; in revised form: 5 May 2010 / Accepted: 10 May 2010 / Published: 25 May 2010 Abstract: There is compelling evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 selective inhibitors have antineoplastic activity, but toxicity from cyclooxygenase (COX) inhibition and the suppression of physiologically important prostaglandins limits their use for cancer chemoprevention. Previous studies as reviewed here suggest that the mechanism for their anticancer properties does not require COX inhibition, but instead involves an off-target effect. In support of this possibility, recent molecular modeling studies have shown that the NSAID sulindac can be chemically modified to selectively design out its COX-1 and COX-2 inhibitory