| Version |
2.5 |
| Creation Date |
2005-06-13 13:24:05 |
| Update Date |
2009-02-19 16:03:39 |
| Primary Accession Number |
DB00227 |
| Secondary Accession Number |
|
| Name |
Lovastatin |
| Drug Type |
- Approved
- Investigational
- Small Molecule
|
| Description |
A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl COA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [PubChem] |
| Synonyms |
- 6 alpha-Methylcompactin
- Lovastatina [Spanish]
- Lovastatine [French]
- Lovastatinum [Latin]
- lovastatin
|
| Brand Names |
- Altocor
- Altoprev
- Artein
- Belvas
- Cholestra
- Closterol
- Colevix
- Hipolip
- Hipovastin
- Lestatin
- Lipdip
- Lipivas
- Lipofren
- Lovalip
- Lovalord
- Lovasterol
- Lovastin
- Lozutin
- Mevacor
- Mevinacor
- Mevlor
- Monacolin K
- Nergadan
- Paschol
- Rodatin
- Rovacor
- Sivlor
- Taucor
- Tecnolip
- Teroltrat
|
| Brand Mixtures |
Not Available |
| Chemical IUPAC Name |
[(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate |
| Chemical Formula |
C24H36O5 |
| Chemical Structure |
 |
| CAS Registry Number |
75330-75-5 |
| InChI Identifier |
InChI=1/C24H36O5/c1-5-15(3)24(27)29-21-11-14(2)10-17-7-6-16(4)20(23(17)21)9-8-19-12-18(25)13-22(26)28-19/h6-7,10,14-16,18-21,23,25H,5,8-9,11-13H2,1-4H3/t14-,15-,16-,18+,19+,20-,21-,23-/m0/s1 |
| InChI Key |
PCZOHLXUXFIOCF-BXMDZJJMBQ |
| KEGG Drug |
D00359  |
| KEGG Compound |
C07074  |
| PubChem Compound |
53232  |
| PubChem Substance |
191104  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA450272  |
| HET ID |
803  |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02243127  |
| RxList Link |
http://www.rxlist.com/cgi/generic3/altocor.htm  |
| PDRhealth Link |
Not Available |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Lovastatin  |
| FDA Label |
|
| Material Safety Data Sheet (MSDS) |
Not Available |
| Synthesis Reference |
R. L. Monaghan et al., U.S. Pat. 4,231,938 (1980) |
| Average Molecular Weight |
404.5396 |
| Monoisotopic Molecular Weight |
404.2563 |
| State |
Solid |
| Melting Point |
174.5 oC |
| Experimental Water Solubility |
0.0004 mg/mL
Source: PhysProp
|
| Predicted Water Solubility |
2.43e-02 mg/mL
Calculated using ALOGPS
|
| Experimental LogP/Hydrophobicity |
4.5
Source: PhysProp
|
| Predicted LogP |
4.11
Calculated using ALOGPS
|
| Experimental LogS |
Not Available |
| Predicted LogS |
-4.22
Calculated using ALOGPS
|
| Experimental Caco2 Permeability |
Not Available |
| pKa/Isoelectric Point |
Not Available |
| Mass Spectrum |
Not Available
|
| MOL File |
Show | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 2D Structure |
|
| 3D Structure |
|
| Experimental PDB ID |
Not Available |
| Isomeric SMILES |
CC[C@H](C)C(=O)O[C@H]1C[C@@H](C)C=C2C=C[C@H](C)[C@H](CC[C@@H]3C[C@@H](O)CC(=O)O3)[C@@H]12 |
| Canonical SMILES |
CCC(C)C(=O)OC1CC(C)C=C2C=CC(C)C(CCC3CC(O)CC(=O)O3)C12 |
| Drug Category |
- Anticholesteremic Agents
- Antineoplastic Agents
- HMG-CoA Reductase Inhibitors
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
|
| ATC Codes |
|
| AHFS Codes |
|
| Indication |
For management as an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels in patients with primary hypercholesterolemia and mixed dyslipidemia; For primary prevention of coronary heart disease |
| Pharmacology |
Lovastatin, an antilipemic agent produced by fermentation of Aspergillus terreus, is the first of a class of lipid-lowering agents known as the HMG-CoA reductase inhibitors. Lovastatin is used to treat hypercholesterolemia, to slow coronary atherosclerosis, and to prevent myocardial infarction and stroke. Lovastatin, like simvastin and unlike pravastatin, is a prodrug, concentrating active drug in the liver during first-pass circulation. |
| Mechanism of Action |
Lovastatin is a lactone that is readily hydrolyzed in vivo to the corresponding b-hydroxyacid, a potent inhibitor of HMG-CoA reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate. The conversion of HMG-CoA to mevalonate is an early step in the biosynthetic pathway for cholesterol. |
| Absorption |
30% |
| Toxicity |
LD50>1000 mg/kg (orally in mice) |
| Protein Binding |
>95% |
| Biotransformation |
hepatic |
| Half Life |
5.3 hours |
| Dosage Forms |
|
| Patient Information |
Show  |
| Contraindications |
Show  |
| Interactions |
Show  |
| Drug Interactions |
| Drug |
Interaction |
| Acenocoumarol |
The statin increases the anticoagulant effect |
| Amprenavir |
Amprenavir can possibly increase the statin toxicity |
| Anisindione |
The statin increases the anticoagulant effect |
| Atazanavir |
Increased risk of myopathy/rhabdomyolysis |
| Azithromycin |
Azithromycin can possibly increase the statin toxicity |
| Bezafibrate |
Increased risk of myopathy/rhabdomyolysis |
| Bosentan |
Bosentan could decrease the statin effect |
| Carbamazepine |
Carbamazepine decreases the effect of the statin |
| Clarithromycin |
The macrolide possibly increases the statin toxicity |
| Colchicine |
Increased risk of rhabdomyolysis with this combination |
| Cyclosporine |
Possible myopathy and rhabdomyolysis |
| Danazol |
Risk of severe myopathy/rhabdomyolysis with this combination |
| Delavirdine |
The NNRT inhibitor increases the effect and toxicity of the statin |
| Dicumarol |
The statin increases the anticoagulant effect |
| Diltiazem |
Diltiazem increases the effect and toxicity of the statin |
| Efavirenz |
The NNRT inhibitor increases the effect and toxicity of the statin |
| Erythromycin |
The macrolide possibly increases the statin toxicity |
| Fenofibrate |
Increased risk of myopathy/rhabdomyolysis |
| Fluconazole |
Increased risk of myopathy/rhabdomyolysis |
| Fosamprenavir |
Amprenavir can possibly increase the statin toxicity |
| Gemfibrozil |
Increased risk of myopathy/rhabdomyolysis |
| Imatinib |
Imatinib increases the effect and toxicity of statin |
| Itraconazole |
Increased risk of myopathy/rhabdomyolysis |
| Josamycin |
The macrolide possibly increases the statin toxicity |
| Ketoconazole |
Increased risk of myopathy/rhabdomyolysis |
| Nefazodone |
Nefazodone increases the effect and toxicity of the statin |
| Nelfinavir |
Nelfinavir increases the effect and toxicity of the statin |
| Nevirapine |
The NNRT inhibitor increases the effect and toxicity of the statin |
| Niacin |
Risk of severe myopathy/rhabdomyolysis with this combination |
| Quinupristin |
This combination presents an increased risk of toxicity |
| Rifabutin |
The rifamycin decreases the effect of statin drug |
| Rifampin |
The rifamycin decreases the effect of statin drug |
| Ritonavir |
Ritonavir increases the effect and toxicity of the statin |
| Tacrolimus |
Tacrolimus increases the effect and toxicity of the statin |
| Telithromycin |
Telithromycin may possibly increase statin toxicity |
| Verapamil |
Verapamil increases the effect and toxicity of statin |
| Warfarin |
The statin increases the anticoagulant effect |
|
| Food Interactions |
- Avoid alcohol.
- Avoid drastic changes in dietary habit.
- Avoid taking with grapefruit juice.
- Take with food, 50% increase in bioavailability when taken with food.
|
| Pathways |
| Name |
SMPDB Link |
KEGG Link |
| Lovastatin Pathway |
SMP00099  |
|
|
| General References |
- Bobek P, Ozdin L, Galbavy S: Dose- and time-dependent hypocholesterolemic effect of oyster mushroom (Pleurotus ostreatus) in rats. Nutrition. 1998 Mar;14(3):282-6. [PubMed
]
- Drugs.com

- Wikipedia

- RxList

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Cytochrome P450 3A4 (CYP3A4)
- Cytochrome P450 2C8 (CYP2C8)
|
| Targets |
- 3-hydroxy-3-methylglutaryl-coenzyme A reductase
|
|
Drug Target 1
[top]
|
| Target 1 ID |
631 |
| Target 1 Name |
3-hydroxy-3-methylglutaryl-coenzyme A reductase |
| Target 1 Synonyms |
- EC 1.1.1.34
- HMG-CoA reductase
|
| Target 1 Gene Name |
HMGCR |
| Target 1 Protein Sequence |
>3-hydroxy-3-methylglutaryl-coenzyme A reductase
MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSS
DIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTG
LNEALPFFLLLIDLSRASTLAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIG
VGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFAR
VLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTADTSKVSLGLDENVSKR
IEPSVSLWQFYLSKMISMDIEQVITLSLALLLAVKYIFFEQTETESTLSLKNPITSPVVT
QKKVPDNCCRREPMLVRNNQKCDSVEEETGINRERKVEVIKPLVAETDTPNRATFVVGNS
SLLDTSSVLVTQEPEIELPREPRPNEECLQILGNAEKGAKFLSDAEIIQLVNAKHIPAYK
LETLMETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGV
AGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRAC
DSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMI
SKGTEKALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREV
LKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITL
MEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLAR
IVCGTVMAGELSLMAALAAGHLVKSHMIHNRSKINLQDLQGACTKKTA
|
| Target 1 Number of Residues |
902 |
| Target 1 Molecular Weight |
97477 |
| Target 1 Theoretical pI |
6.72 |
| Target 1 GO Classification |
|
Function
|
hydroxymethylglutaryl-CoA reductase (NADPH) activity
hydroxymethylglutaryl-CoA reductase (NADPH) activity
catalytic activity
oxidoreductase activity
oxidoreductase activity, acting on CH-OH group of donors
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
hydroxymethylglutaryl-CoA reductase (NADPH) activity |
|
Process
|
primary metabolism
lipid metabolism
physiological process
metabolism
biosynthesis |
|
Component
|
organelle membrane
endoplasmic reticulum membrane
cell
membrane
intrinsic to membrane
integral to membrane |
|
| Target 1 General Function |
Lipid transport and metabolism |
| Target 1 Specific Function |
This transmembrane glycoprotein is involved in the control of cholesterol biosynthesis. It is the rate-limiting enzyme of sterol biosynthesis |
| Target 1 Pathways |
| Name |
SMPDB Link |
KEGG Link |
| Biosynthesis of steroids |
|
map00100  |
|
| Target 1 Reactions |
- (R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
|
| Target 1 Pfam Domain Function |
|
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
- 10-39
- 57-78
- 90-114
- 124-149
- 160-187
- 192-220
- 315-339
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
306865  |
| Target 1 UniProtKB/Swiss-Prot ID |
P04035  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
HMDH_HUMAN  |
| Target 1 PDB ID |
1HWL  |
| Target 1 PDB File |
Show |
| Target 1 3D Structure |
|
| Target 1 Cellular Location |
- Endoplasmic reticulum
- endoplasmic reticulum membrane
- multi-pass membrane protein. Peroxisome
- pero
|
| Target 1 Gene Sequence |
>2667 bp
ATGTTGTCAAGACTTTTTCGAATGCATGGCCTCTTTGTGGCCTCCCATCCCTGGGAAGTC
ATAGTGGGGACAGTGACACTGACCATCTGCATGATGTCCATGAACATGTTTACTGGTAAC
AATAAGATCTGTGGTTGGAATTATGAATGTCCAAAGTTTGAAGAGGATGTTTTGAGCAGT
GACATTATAATTCTGACAATAACACGATGCATAGCCATCCTGTATATTTACTTCCAGTTC
CAGAATTTACGTCAACTTGGATCAAAATATATTTTGGGTATTGCTGGCCTTTTCACAATT
TTCTCAAGTTTTGTATTCAGTACAGTTGTCATTCACTTCTTAGACAAAGAATTGACAGGC
TTGAATGAAGCTTTGCCCTTTTTCCTACTTTTGATTGACCTTTCCAGAGCAAGCACATTA
GCAAAGTTTGCCCTCAGTTCCAACTCACAGGATGAAGTAAGGGAAAATATTGCTCGTGGA
ATGGCAATTTTAGGTCCTACGTTTACCCTCGATGCTCTTGTTGAATGTCTTGTGATTGGA
GTTGGTACCATGTCAGGGGTACGTCAGCTTGAAATTATGTGCTGCTTTGGCTGCATGTCA
GTTCTTGCCAACTACTTCGTGTTCATGACTTTCTTCCCAGCTTGTGTGTCCTTGGTATTA
GAGCTTTCTCGGGAAAGCCGCGAGGGTCGTCCAATTTGGCAGCTCAGCCATTTTGCCCGA
GTTTTAGAAGAAGAAGAAAATAAGCCGAATCCTGTAACTCAGAGGGTCAAGATGATTATG
TCTCTAGGCTTGGTTCTTGTTCATGCTCACAGTCGCTGGATAGCTGATCCTTCTCCTCAA
AACAGTACAGCAGATACTTCTAAGGTTTCATTAGGACTGGATGAAAATGTGTCCAAGAGA
ATTGAACCAAGTGTTTCCCTCTGGCAGTTTTATCTCTCTAAAATGATCAGCATGGATATT
GAACAAGTTATTACCCTAAGTTTAGCTCTCCTTCTGGCTGTCAAGTACATCTTCTTTGAA
CAAACAGAGACAGAATCTACACTCTCATTAAAAAACCCTATCACATCTCCTGTAGTGACA
CAAAAGAAAGTCCCAGACAATTGTTGTAGACGTGAACCTATGCTGGTCAGAAATAACCAG
AAATGTGATTCAGTAGAGGAAGAGACAGGGATAAACCGAGAAAGAAAAGTTGAGGTTATA
AAACCCTTAGTGGCTGAAACAGATACCCCAAACAGAGCTACATTTGTGGTTGGTAACTCC
TCCTTACTCGATACTTCATCAGTACTGGTGACACAGGAACCTGAAATTGAACTTCCCAGG
GAACCTCGGCCTAATGAAGAATGTCTACAGATACTTGGGAATGCAGAGAAAGGTGCAAAA
TTCCTTAGTGATGCTGAGATCATCCAGTTAGTCAATGCTAAGCATATCCCAGCCTACAAG
TTGGAAACTCTGATGGAAACTCATGAGCGTGGTGTATCTATTCGCCGACAGTTACTTTCC
AAGAAGCTTTCAGAACCTTCTTCTCTCCAGTACCTACCTTACAGGGATTATAATTACTCC
TTGGTGATGGGAGCTTGTTGTGAGAATGTTATTGGATATATGCCCATCCCTGTTGGAGTG
GCAGGACCCCTTTGCTTAGATGAAAAAGAATTTCAGGTTCCAATGGCAACAACAGAAGGT
TGTCTTGTGGCCAGCACCAATAGAGGCTGCAGAGCAATAGGTCTTGGTGGAGGTGCCAGC
AGCCGAGTCCTTGCAGATGGGATGACTCGTGGCCCAGTTGTGCGTCTTCCACGTGCTTGT
GACTCTGCAGAAGTGAAAGCCTGGCTCGAAACATCTGAAGGGTTCGCAGTGATAAAGGAG
GCATTTGACAGCACTAGCAGATTTGCACGTCTACAGAAACTTCATACAAGTATAGCTGGA
CGCAACCTTTATATCCGTTTCCAGTCCAGGTCAGGGGATGCCATGGGGATGAACATGATT
TCAAAGGGTACAGAGAAAGCACTTTCAAAACTTCACGAGTATTTCCCTGAAATGCAGATT
CTAGCCGTTAGTGGTAACTATTGTACTGACAAGAAACCTGCTGCTATAAATTGGATAGAG
GGAAGAGGAAAATCTGTTGTTTGTGAAGCTGTCATTCCAGCCAAGGTTGTCAGAGAAGTA
TTAAAGACTACCACAGAGGCTATGATTGAGGTCAACATTAACAAGAATTTAGTGGGCTCT
GCCATGGCTGGGAGCATAGGAGGCTACAACGCCCATGCAGCAAACATTGTCACCGCCATC
TACATTGCCTGTGGACAGGATGCAGCACAGAATGTTGGTAGTTCAAACTGTATTACTTTA
ATGGAAGCAAGTGGTCCCACAAATGAAGATTTATATATCAGCTGCACCATGCCATCTATA
GAGATAGGAACGGTGGGTGGTGGGACCAACCTACTACCTCAGCAAGCCTGTTTGCAGATG
CTAGGTGTTCAAGGAGCATGCAAAGATAATCCTGGGGAAAATGCCCGGCAGCTTGCCCGA
ATTGTGTGTGGGACCGTAATGGCTGGGGAATTGTCACTTATGGCAGCATTGGCAGCAGGA
CATCTTGTCAAAAGTCACATGATTCACAACAGGTCGAAGATCAATTTACAAGACCTCCAA
GGAGCTTGCACCAAGAAGACAGCCTGA
|
| Target 1 GenBank Gene ID |
|
| Target 1 GeneCard ID |
HMGCR  |
| Target 1 GenAtlas ID |
HMGCR  |
| Target 1 HGNC ID |
HGNC:5006  |
| Target 1 Chromosome Location |
5 |
| Target 1 Locus |
5q13.3-q14 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed
]
- Istvan ES, Palnitkar M, Buchanan SK, Deisenhofer J: Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis. EMBO J. 2000 Mar 1;19(5):819-30. [PubMed
]
- Luskey KL, Stevens B: Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation. J Biol Chem. 1985 Aug 25;260(18):10271-7. [PubMed
]
|
| Target 1 Drug References |
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed
]
- Abe Y, Suzuki T, Ono C, Iwamoto K, Hosobuchi M, Yoshikawa H: Molecular cloning and characterization of an ML-236B (compactin) biosynthetic gene cluster in Penicillium citrinum. Mol Genet Genomics. 2002 Jul;267(5):636-46. Epub 2002 Jun 28. [PubMed
]
- Miyazaki A, Koieyama T, Shimada Y, Kikuchi T, Nezu H, Ito K, Kasanuki N, Koga T: Effects of pravastatin sodium on mevalonate metabolism in common marmosets. J Biochem (Tokyo). 2002 Sep;132(3):395-400. [PubMed
]
- Buxbaum JD, Geoghagen NS, Friedhoff LT: Cholesterol depletion with physiological concentrations of a statin decreases the formation of the Alzheimer amyloid Abeta peptide. J Alzheimers Dis. 2001 Apr;3(2):221-229. [PubMed
]
- Baranova NA, Kreier VG, Egorov NS: [Concentration on Diapak C 16 capsules of lovastatin, mevinolinic acid and other inhibitors of biosynthesis of sterins produced by Penicillium citrinum 89] Antibiot Khimioter. 2002;47(4):3-6. [PubMed
]
- Farina HG, Bublik DR, Alonso DF, Gomez DE: Lovastatin alters cytoskeleton organization and inhibits experimental metastasis of mammary carcinoma cells. Clin Exp Metastasis. 2002;19(6):551-9. [PubMed
]
|