Lapaquistat

Drugbox
IUPAC_name = 1-{ [(3"R",5"S")-1-(3-hydroxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl) -2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl] acetyl}piperidine-4-acetic acid

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CAS_number = 189059-71-0
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C=31 | H=39 | Cl=1| N=2 | O=8
molecular_weight = 603.103 g/mol
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Lapaquistat (TAK-475) is a cholesterol-lowering drug. Unlike statins which inhibit HMG-CoA reductase, lapaquistat metabolites inhibit squalene synthase which is further downstream in the synthesis of cholesterol. It is hoped that side effects can be reduced by not disturbing the mevalonate pathway which is important for other biochemical molecules besides cholesterol.However, there is increasing evidence that statins (which inhibit the mevalonate pathway) may be clinically useful because they affect these other molecules (including protein prenylation)cite journal |author=Greenwood J, Steinman L, Zamvil SS |title=Statin therapy and autoimmune disease: from protein prenylation to immunomodulation |journal=Nat. Rev. Immunol. |volume=6 |issue=5 |pages=358–70 |year=2006 |month=May |pmid=16639429 |doi=10.1038/nri1839 |url=] .

On March 28, 2008, Takeda halted further development of lapaquistat. [ [http://www.takeda.com/press/article_29153.html Takeda Pharmaceutical Company Limited press release - Discontinuation of Development of TAK-475, A Compound for Treatment of Hypercholesterolemia] ]

References

*cite journal|author=Davidson MH| title=Squalene synthase inhibition: a novel target for the management of dyslipidemia| journal=Curr Atheroscler Rep| year=2007| month=Jan| volume=9| issue=1| pages=78–80| pmid=17169251| doi=10.1007/BF02693932