Therapeutic Targets Database
BIDD Pharmainformatics Databases
 
   
 

 

TTD Target ID: TTDS00195

Target Information
Name3-hydroxy-3-methylglutaryl-coenzyme A reductase    
Type of targetSuccessful target    
SynonymsHMG coA reductase    
HMG-CoA reductase    
DiseaseAtherosclerosis    [1]
Cardiovascular disease, unspecified    [2]
Cervical cancer    [3]
Coronary heart disease    [4]
Dyslipidemia    [5]
Head and neck squamous cell carcinomas    [3]
Hypercholesterolemia    [6]
Hypertriglyceridemia    [7]
Myocardial infarction    [8]
Drug(s)AtorvastatinApprovedHypercholesterolemia[9]
FluvastatinApprovedHypercholesterolemia[9]
LovastatinApprovedHypercholesterolemia[3]
PitavastatinApprovedHyperlipidaemia and mixed dyslipidaemia[10][11]
PravastatinApprovedHypercholesterolemia[12]
RosuvastatinApprovedHypercholesterolemia[4]
SimvastatinApprovedHypercholesterolemia[9]
PravigardMarketedMyocardial infarction, cerebrovascular ischaemia[13]
SimvistatinMarketedAntihyperlipidaemic[13]
Crestor/TriLipixMAA and NDA FiledDyslipidaemia[14]
MK-0524BPhase IIIAtherosclerosis[15][16]
RosuvastatinPhase IIIElevated CRP[14]
StatinsPhase I/IIMultiple myeloma[17][11]
SimvistatinPhase IHepatitis B[13]
PitavastatinDiscontinued in Phase IIIHyperlipidemia[10][11]
HMG-CoA reductase inhibitorPreclinicalChemotherapy- or radiotherapy-induced mucositis[18]
BioChemical ClassOxidoreductases acting on the CH-OH group of donors    
EC NumberEC 1.1.1.34
PathwayBiosynthesis of steroids
Metabolic pathways
UniProt IDP04035
PDB Structure1HW9; 1HWI; 1HWJ; 1HWK; 1HWL; 2Q1L; 2Q6B; 2Q6C.    
FunctionThis transmembrane glycoprotein is involved in the control of cholesterol biosynthesis. It is the rate-limiting enzyme of sterol biosynthesis.    
SequenceMLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSS DIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTG LNEALPFFLLLIDLSRASTLAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIG VGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFAR VLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTADTSKVSLGLDENVSKR IEPSVSLWQFYLSKMISMDIEQVITLSLALLLAVKYIFFEQTETESTLSLKNPITSPVVT QKKVPDNCCRREPMLVRNNQKCDSVEEETGINRERKVEVIKPLVAETDTPNRATFVVGNS SLLDTSSVLVTQEPEIELPREPRPNEECLQILGNAEKGAKFLSDAEIIQLVNAKHIPAYK LETLMETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGV AGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRAC DSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMI SKGTEKALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREV LKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITL MEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLAR IVCGTVMAGELSLMAALAAGHLVKSHMIHNRSKINLQDLQGACTKKTA
Related US Patent6,245,535
6,420,417
6,468,780
6,492,410
6,534,537
6,534,540
6,541,511
6,569,461
6,583,295
6,620,821
6,627,636
6,642,268
6,680,341
Target ValidationClick to Find Target Validation Information.    
QSAR ModelClick to Find Target QSAR Model.    
Inhibitor (E)-5-octadecen-7,9-diynoic acid[19]
(E)-octadecan-9-ynoic acid[19]
(R)-Mevalonate[20]
(Z)-5-octadecen-7,9-diynoic acid[19]
(Z)-7-octedecan-9-ynoic acid[19]
1,4-Dithiothreitol[20]
2'-Monophosphoadenosine 5'-Diphosphoribose[20]
3- (1,3 dodecadiynyl)-6-oxiranebutanoic acid[19]
3-Hydroxy-3-Methyl-Glutaric Acid[20]
6-hydroxy-7,9-octadecadiynoic acid[19]
7,9-octadecadiynoic acid[19]
7,9-tetradecadiynoic acid[19]
9-octadecynoic acid[19]
Adenosine-5'-Diphosphate[21]
Atorvastatin[9]
Cerivastatin[22]
Coenzyme A[20]
Crestor/TriLipix[14]
F (4-Fluoro)VAE[23]
Fluvastatin[9]
GFPDGG[23]
GFPEGG[23]
GFPTGG[23]
GLPTGG[23]
HMG-CoA reductase inhibitor[18]
Lovastatin[3]
MK-0524B[15][16]
Meglutol[24]
NK-104[25]
Nicotinamide-Adenine-Dinucleotide[20]
PF-3052334[26]
PITAVASTATIN CALCIUM[27]
Pitavastatin[10][11]
Pravastatin[12]
Pravigard[13]
Rosuvastatin[4]
Rosuvastatin[14]
Simvastatin[9]
Simvistatin[13]
Statins[17][11]
atorvastatin calcium[27]
rosuvastatin calcium[27]
AntagonistMevastatin[28]
MultitargetPravigard[13]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1The key enzyme of cholesterol synthesis pathway: HMG-CoA reductase and disease. Sheng Li Ke Xue Jin Zhan. 1999 Jan;30(1):5-9. To Reference
Ref 2Inhibitors of HMG CoA reductase: new modes of action, new indications?. Therapie. 2000 Jan-Feb;55(1):43-9. To Reference
Ref 3Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas. Neoplasia. 2002 Jul-Aug;4(4):337-46. To Reference
Ref 4New dimension of statin action on ApoB atherogenicity. Clin Cardiol. 2003 Jan;26(1 Suppl 1):I7-10. To Reference
Ref 5Treatment of diabetic dyslipidemia. Am J Cardiol. 1998 Feb 26;81(4A):47B-51B. To Reference
Ref 6Treating hypercholesterolemia: looking forward. Clin Cardiol. 2003 Jan;26(1 Suppl 1):I21-8. To Reference
Ref 7Identification and treatment of hypertriglyceridemia as a risk factor for coronary heart disease. Curr Cardiol Rep. 1999 Sep;1(3):233-7. To Reference
Ref 8Cost-effectiveness of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor therapy in older patients with myocardial infarction. Ann Intern Med. 2000 May 16;132(10):780-7. To Reference
Ref 9Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64. To Reference
Ref 10Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92. To Reference
Ref 11Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81. To Reference
Ref 12A randomized, double-blind trial comparing the efficacy and safety of pitavastatin versus pravastatin in patients with primary hypercholesterolemia. Atherosclerosis. 2002 Jun;162(2):373-9. To Reference
Ref 13Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90. To Reference
Ref 14AstraZeneca. Product Development Pipeline. January 29 2009. To Reference
Ref 15Merck. Product Development Pipeline. July 15 2009. To Reference
Ref 16Merck. Report of Merck. 2009. To Reference
Ref 17Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127. To Reference
Ref 18Emerging drugs for chemotherapy-induced mucositis. Expert Opin Emerg Drugs. 2008 Sep;13(3):511-22. To Reference
Ref 19J. Nat. Prod. 52(1):153-161 (1989) To Reference
Ref 20Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference
Ref 21Nucleic Acids Res. 2011 January; 39(Database issue): D1035¨CD1041. DrugBank 3.0: a comprehensive resource for ¡®Omics¡¯ research on drugs To Reference
Ref 22HMG-CoA reductase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats. Stroke. 2003 Jan;34(1):157-63. To Reference
Ref 23Bioorg Med Chem. 2008 Feb 1;16(3):1309-18. Epub 2007 Oct 23.Binding effect and design of a competitive inhibitory peptide for HMG-CoA reductase through modeling of an active peptide backbone. To Reference
Ref 24Bioorg Med Chem Lett. 2005 Feb 15;15(4):989-94.Molecular docking of the highly hypolipidemic agent alpha-asarone with the catalytic portion of HMG-CoA reductase. To Reference
Ref 25Cholesterol-lowering effect of NK-104, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, in guinea pig model of hyperlipidemia. Arzneimittelforschung. 2001;51(3):197-203. To Reference
Ref 26J Med Chem. 2008 Jan 10;51(1):31-45. Epub 2007 Dec 12.Substituted pyrazoles as hepatoselective HMG-CoA reductase inhibitors: discovery of (3R,5R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxyheptanoic acid (PF-3052334) as a candidate for the treatment of hypercholesterolemia. To Reference
Ref 27Bioorg Med Chem. 2007 Dec 15;15(24):7809-29. Epub 2007 Aug 28.Synthesis and HMG CoA reductase inhibition of 4-thiophenyl quinolines as potential hypocholesterolemic agents. To Reference
Ref 28Kocarek TA, Dahn MS, Cai H, Strom SC, Mercer-Haines NA: Regulation of CYP2B6 and CYP3A expression by hydroxymethylglutaryl coenzyme A inhibitors in primary cultured human hepatocytes. Drug Metab Dispos. 2002 Dec;30(12):1400-5. To Reference



 

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