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Systematic (IUPAC) name
(1-{[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl}piperidin-4-yl)acetic acid
Clinical data
189059-71-0 N
PubChem CID 9960389
ChemSpider 8135996 YesY
Chemical data
Formula C31H39ClN2O8
603.103 g/mol
 N (what is this?)  (verify)

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).[1]

On March 28, 2008, Takeda halted further development of lapaquistat.[2] While effective at lowering low-density lipoprotein cholesterol in a dose-dependent manner, development of the drug was ceased over potential hepatic safety issues. [3]


  1. ^ Greenwood J, Steinman L, Zamvil SS (May 2006). "Statin therapy and autoimmune disease: from protein prenylation to immunomodulation". Nat. Rev. Immunol. 6 (5): 358–70. doi:10.1038/nri1839. PMID 16639429. 
  2. ^ Takeda Pharmaceutical Company Limited press release - Discontinuation of Development of TAK-475, A Compound for Treatment of Hypercholesterolemia
  3. ^ Stein, Evan et al. (April 25, 2011). "Lapaquistat Acetate, Development of a Squalene Synthase Inhibitor for the Treatment of Hypercholesterolemia". Circulation 123 (18): 1974–1985. doi:10.1161/CIRCULATIONAHA.110.975284. 
  • Davidson MH (January 2007). "Squalene synthase inhibition: a novel target for the management of dyslipidemia". Curr Atheroscler Rep 9 (1): 78–80. doi:10.1007/BF02693932. PMID 17169251.