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OSU-03012
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OSU-03012 : ウィキペディア英語版
OSU-03012

OSU-03012 (AR-12) is a celecoxib derivative with anticancer and anti-microbial activity. Unlike celecoxib, OSU-03012 does not inhibit COX, but inhibits several other important enzymes instead which may be useful in the treatment of some forms of cancer,〔Booth L, Cruickshanks N, Ridder T, Chen CS, Grant S, Dent P. OSU-03012 interacts with lapatinib to kill brain cancer cells. ''Cancer Biology and Therapy''. 2012 Dec;13(14):1501-11. doi: 10.4161/cbt.22275 PMID 22990204〕〔Ma Y, McCarty SK, Kapuriya NP, Brendel VJ, Wang C, Zhang X, Jarjoura D, Saji M, Chen CS, Ringel MD. Development of p21 activated kinase-targeted multikinase inhibitors that inhibit thyroid cancer cell migration. ''Journal of Clinical Endocrinology and Metabolism''. 2013 Aug;98(8):E1314-22. doi: 10.1210/jc.2012-3937 PMID 23709653〕 while also having antifungal activity via disruption of phosphoinositide-dependent kinase-1 activity.〔(OSU-03012, a non-cox inhibiting celecoxib derivative, induces apoptosis of human esophageal carcinoma cells through a p53/Bax/cytochrome c/caspase-9-dependent pathway )〕 When combined with PDE5 inhibitors such as sildenafil or tadalafil, OSU-03012 was found to show enhanced anti-tumour,〔Booth L, Roberts JL, Cruickshanks N, Grant S, Poklepovic A, Dent P. Regulation of OSU-03012 toxicity by ER stress proteins and ER stress-inducing drugs. ''Molecular Cancer Therapeutics''. 2014 Oct;13(10):2384-98. doi: 10.1158/1535-7163.MCT-14-0172 PMID 25103559〕 antibiotic and antiviral activity against a wide variety of organisms, with this activity thought to be mediated via inhibition of the chaperone protein BiP.〔Paul Dent et al. GRP78 / BiP / HSPA5 / Dna K is a universal therapeutic target for human disease. ''Journal of Cellular Physiology'' 2014 DOI: 10.1002/jcp.24919〕
==Orphan drug designation==

The European Commission has designated AR-12 as an orphan drug for use in combination with other drugs for treatment of two infections diseases, cryptococcosis and tularaemia. AR-12 received an orphan drug designation in combination with the antifungal drug fluconazole for cryptococcosis of the brain. It also received this designation for tularaemia in combination with the antibacterial drug gentamicin.〔(Arno Therapeutics Inc receives european orphan drug designation for AR-12 to reat two infectious diseases. ) Reuters, 30 Apr 2015.〕

抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)
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