KEGG   PATHWAY: map07024
Entry
map07024          Drug      Pathway                                

Name
HMG-CoA reductase inhibitors
Description
HMG-CoA reductase inhibitors, also known as statins, are a class of cholesterol lowering drugs that target HMG-CoA reductase in the mevalonate pathway. In 1971 Akira Endo and his team working for the Japanese pharmaceutical company Sankyo started a project to search for microbial metabolites that would inhibit HMG-CoA reductase, the rate-limiting enzyme in the cholesterol biosynthesis, hoping that certain microorganisms would produce such inhibitors as a weapon against other microbes. After screening 6,000 microbial strains mevastatin was discovered from Penicillium citrinum, but the clinical trial of mevastatin was not completed because of its toxicity. The first successful statin was lovastatin isolated from Aspergillus terreus by Merck, which had repeated Sankyo's approach to microbial screening. Following the first generation statins that are based on natural products, the second and the third generation statins were developed using chemical synthesis.
Class
Pathway map
map07024  HMG-CoA reductase inhibitors
map07024

Compound
C00356  (S)-3-Hydroxy-3-methylglutaryl-CoA
C13334  Pitavastatin
C13963  Mevastatin
D00359  Lovastatin (USP/INN)
D00434  Simvastatin (JP18/USP/INN)
D00887  Atorvastatin calcium anhydorous
D00889  Cerivastatin sodium (JAN/USAN)
D00892  Fluvastatin sodium (JAN/USP)
D00893  Pravastatin sodium (JP18/USP)
D01862  Pitavastatin calcium (JAN)
D01915  Rosuvastatin calcium (JP18/USP)
D02258  Atorvastatin calcium (USP)
D07474  Atorvastatin (INN)
D07661  Cerivastatin (INN)
D07983  Fluvastatin (INN)
D08410  Pravastatin (INN)
D08492  Rosuvastatin (INN)
Reference
(Japanese)
  Authors
Sano T, Naito T, Kubo T (eds).
  Title
[Medicinal Chemistry, an Introduction (7th ed)] (In Japanese)
  Journal
Nankodo (2002)
Reference
(Japanese)
  Authors
Fukai S.
  Title
[New Drugs Today (6th ed)] (In Japanese)
  Journal
Jiho (1995)
Reference
  Authors
Walter S.
  Title
Drug Discovery: A History
  Journal
Wiley (2005)
Reference
(Japanese)
  Authors
Japan Pharmaceutical Association (ed).
  Title
[Face of Medecine: Structure Activity Relationship] (In Japanese)
  Journal
Yakuji Nippo (1999)
Reference
(Japanese)
  Authors
Noguchi S, Hibino S (eds).
  Title
[Medicinal Chemistry: Bridge Between Biology (3rd ed)] (In Japanese)
  Journal
Hirokawa (2002)
Reference
(Japanese)
  Authors
Teramoto T (ed).
  Title
[Statins Q & A] (In Japanese)
  Journal
Iyaku journal (2001)
Reference
(Japanese)
  Authors
Takamisawa I, Shiba M.
  Title
[Structure, activity and metabolism of statins.] (In Japanese)
  Journal
Chiryogaku 36(5):35-40 (2002)
Reference
PMID:9892578
  Authors
Furberg CD
  Title
Natural statins and stroke risk.
  Journal
Circulation 99:185-8 (1999)
DOI:10.1161/01.CIR.99.2.185
Reference
  Authors
Veillard NR, Mach F.
  Title
Statins: the new aspirin?
  Journal
Cell Mol Life Sci 59:1771-86 (2002)
DOI:10.1007/PL00012505
Reference
  Authors
Endo A.
  Title
The discovery and development of HMG-CoA reductase inhibitors. 1992.
  Journal
Atheroscler Suppl 5:67-80 (2004)
DOI:10.1016/j.atherosclerosissup.2004.08.026
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