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Identification
Name Lovastatin
Accession Number DB00227 (APRD00370)
Type small molecule
Groups approved
Description

Lovastatin is a cholesterol-lowering agent that belongs to the class of medications called statins. It was the second agent of this class discovered. It was discovered by Alfred Alberts and his team at Merck in 1978 after screening only 18 compounds over 2 weeks. The agent, also known as mevinolin, was isolated from the fungi Aspergillus terreus. Research on this compound was suddenly shut down in 1980 and the drug was not approved until 1987. Interesting, Akira Endo at Sankyo Co. (Japan) patented lovastatin isolated from Monascus ruber four months before Merck. Lovastatin was found to be 2 times more potent than its predecessor, mevastatin, the first discovered statin. Like mevastatin, lovastatin is structurally similar to hydroxymethylglutarate (HMG), a substituent of HMG-Coenzyme A (HMG-CoA), a substrate of the cholesterol biosynthesis pathway via the mevalonic acid pathway. Lovastatin is a competitive inhibitor of HMG-CoA reductase with a binding affinity 20,000 times greater than HMG-CoA. Lovastatin differs structurally from mevastatin by a single methyl group at the 6’ position. Lovastatin is a prodrug that is activated by in vivo hydrolysis of the lactone ring. It, along with mevastatin, has served as one of the lead compounds for the development of the synthetic compounds used today.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
6 alpha-Methylcompactin
Lovastatina [Spanish]
Lovastatine [French]
Lovastatinum [Latin]
Salts Not Available
Brand names
Name Company
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
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Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Anticholesteremic Agents
  • HMG-CoA Reductase Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
CAS number 75330-75-5
Weight Average: 404.5396
Monoisotopic: 404.256274262
Chemical Formula C24H36O5
InChI Key InChIKey=PCZOHLXUXFIOCF-BXMDZJJMSA-N
InChI
InChI=1S/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
Plain Text
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
SMILES
[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H]1C[C@@H](O)CC(=O)O1)OC(=O)[C@@H](C)CC
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Statins
Substructures
  • Statins
  • Carboxylic Acids and Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Pyrans
  • Acetates
  • Lactones
  • Ethers
  • Isoprenes
  • Heterocyclic compounds
  • Alcohols and Polyols
  • Cyclohexenes and Derivatives
Pharmacology
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 and to slow progression of coronary atherosclerosis in patients with coronary heart disease.
Pharmacodynamics The primary cause of cardiovascular disease is atherosclerotic plaque formation. Sustained elevations of cholesterol in the blood increase the risk of cardiovascular disease. Lovastatin lowers hepatic cholesterol synthesis by competitively inhibiting HMG-CoA reductase, the enzyme that catalyzes the rate-limiting step in the cholesterol biosynthesis pathway via the mevalonic acid pathway. Decreased hepatic cholesterol levels causes increased uptake of low density lipoprotein (LDL) cholesterol and reduces cholesterol levels in the circulation. At therapeutic doses, lovastatin decreases serum LDL cholesterol by 29-32%, increases high density lipoprotein (HDL) cholesterol by 4.6-7.3%, and decrease triglyceride levels by 2-12%. HDL cholesterol is thought to confer protective effects against CV disease, whereas high LDL and triglyceride levels are associated with higher risk of disease.
Mechanism of action Lovastatin is structurally similar to the HMG, a substituent of the endogenous substrate of HMG-CoA reductase. Lovastatin is a prodrug that is activated in vivo via hydrolysis of the lactone ring. The hydrolyzed lactone ring mimics the tetrahedral intermediate produced by the reductase allowing the agent to bind with 20,000 times greater affinity than its natural substrate. The bicyclic portion of lovastatin binds to the coenzyme A portion of the active site.
Absorption < 5%. Time to peak serum concentration is 2-4 hours.
Volume of distribution Not Available
Protein binding > 95%
Metabolism Undergoes first pass hydrolysis to active metabolites β-hydroxyacid and 6'-hydroxy dervative.
Route of elimination Lovastatin undergoes extensive first-pass extraction in the liver, its primary site of action, with subsequent excretion of drug equivalents in the bile. 83% of the orally administered dose is excreted in bile and 10% is excreted in urine.
Half life 5.3 hours
Clearance Not Available
Toxicity LD50>1000 mg/kg (orally in mice)
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00099 Lovastatin Pathway SMP00099
Pharmacoeconomics
Manufacturers
  • Andrx labs llc
  • Actavis elizabeth llc
  • Apotex inc
  • Carlsbad technology inc
  • Lupin ltd
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Merck research laboratories div merck co inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral 10 mg
Tablet Oral 20 mg
Tablet Oral 40 mg
Prices
Unit description Cost Unit
Altoprev 60 mg 24 Hour tablet 7.99 USD tablet
Altoprev 60 mg tablet 7.74 USD tablet
Altoprev 20 mg 24 Hour tablet 6.88 USD tablet
Altoprev 20 mg tablet 6.61 USD tablet
Mevacor 40 mg tablet 4.57 USD tablet
Altoprev 40 mg tablet 4.41 USD tablet
Lovastatin 40 mg tablet 4.36 USD tablet
Altoprev 10 mg 24 Hour tablet 3.07 USD tablet
Mevacor 20 mg tablet 2.53 USD tablet
Lovastatin 20 mg tablet 2.42 USD tablet
Altocor 20 mg 24 Hour tablet 2.36 USD tablet
Apo-Lovastatin 40 mg Tablet 2.11 USD tablet
Co Lovastatin 40 mg Tablet 2.11 USD tablet
Mylan-Lovastatin 40 mg Tablet 2.11 USD tablet
Novo-Lovastatin 40 mg Tablet 2.11 USD tablet
Pms-Lovastatin 40 mg Tablet 2.11 USD tablet
Ran-Lovastatin 40 mg Tablet 2.11 USD tablet
Ratio-Lovastatin 40 mg Tablet 2.11 USD tablet
Sandoz Lovastatin 40 mg Tablet 2.11 USD tablet
Mevacor 10 mg tablet 1.65 USD tablet
Lovastatin 10 mg tablet 1.37 USD tablet
Apo-Lovastatin 20 mg Tablet 1.14 USD tablet
Co Lovastatin 20 mg Tablet 1.14 USD tablet
Mylan-Lovastatin 20 mg Tablet 1.14 USD tablet
Novo-Lovastatin 20 mg Tablet 1.14 USD tablet
Pms-Lovastatin 20 mg Tablet 1.14 USD tablet
Ran-Lovastatin 20 mg Tablet 1.14 USD tablet
Ratio-Lovastatin 20 mg Tablet 1.14 USD tablet
Sandoz Lovastatin 20 mg Tablet 1.14 USD tablet
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DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6080778 1998-03-23 2018-03-23
United States 5916595 1997-12-12 2017-12-12
Properties
State solid
Experimental Properties
Property Value Source
melting point 174.5 °C Not Available
water solubility 0.0004 mg/mL Not Available
logP 4.26 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 2.43e-02 g/l ALOGPS
logP 4.11 ALOGPS
logP 3.9 ChemAxon
logS -4.2 ALOGPS
pKa (strongest acidic) 14.91 ChemAxon
pKa (strongest basic) -2.8 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 72.83 ChemAxon
rotatable bond count 7 ChemAxon
refractivity 113.18 ChemAxon
polarizability 46.11 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. 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
External Links
Resource Link
KEGG Drug D00359 Link_out
KEGG Compound C07074 Link_out
PubChem Compound 53232 Link_out
PubChem Substance 46508223 Link_out
ChemSpider 48085 Link_out
ChEBI 40303 Link_out
ChEMBL 40303 Link_out
Therapeutic Targets Database DAP000551 Link_out
PharmGKB PA450272 Link_out
IUPHAR 2739 Link_out
Guide to Pharmacology 2739 Link_out
HET 803 Link_out
Drug Product Database 2243127 Link_out
RxList http://www.rxlist.com/cgi/generic3/altocor.htm Link_out
Drugs.com http://www.drugs.com/cdi/lovastatin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Lovastatin Link_out
ATC Codes
  • C10AA02
AHFS Codes
  • 24:06.08
PDB Entries Not Available
FDA label show (126 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Acenocoumarol Lovastatin may increase the anticoagulant effect of acenocoumarol. Monitor for changes in the therapeutic and adverse effects of acenocoumarol if lovastatin is initiated, discontinued or dose changed.
Amprenavir Amprenavir may increase the serum concentration of the lovastatin. Concomitant therapy is contraindicated.
Anisindione Lovastatin may increase the anticoagulant effect of anisindione. Monitor for changes in the therapeutic and adverse effects of anisindione if lovastatin if initiated, discontinued or dose changed.
Atazanavir Atazanavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
Azithromycin The macrolide antibiotic, azithromycin, may increase the serum concentration of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if azithromycin is initiated, discontinued or dose changed.
Bezafibrate Increased risk of myopathy/rhabdomyolysis
Bosentan Bosentan may decrease the serum concentration of lovastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if bosentan is initiated, discontinued or dose changed.
Carbamazepine Carbamazepine, a p-glycoprotein inducer and strong CYP3A4 inducer, may decrease the effect of lovastatin by increasing its efflux and metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if carbamazepine is initiated, discontinued or dose changed.
Clarithromycin The macrolide, clarithromycin, may increase the toxicity of the statin, lovastatin.
Colchicine Increased risk of rhabdomyolysis with this combination
Cyclosporine Possible myopathy and rhabdomyolysis
Danazol Risk of severe myopathy/rhabdomyolysis with this combination
Darunavir Darunavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
Delavirdine Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if delavirdine is initiated, discontinued or dose changed.
Dicumarol Lovastatin may increase the anticoagulant effect dicumarol. Monitor for changes in the therapeutic and adverse effects of dicumarol if lovastatin is initiated, discontinued or dose changed.
Diltiazem Diltiazem may increase the serum concentration of lovastatin. Lovastatin may increase the serum concentration of diltiazem. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.
Efavirenz Efavirenz may decrease the serum concentration of lovastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if efavirenz is initiated, discontinued or dose changed.
Erythromycin The macrolide, erythromycin, may increase the toxicity of the statin, lovastatin.
Fenofibrate Increased risk of myopathy/rhabdomyolysis
Fluconazole Increased risk of myopathy/rhabdomyolysis
Fosamprenavir Fosamprenavir, a strong CYP3A4 inhibitor, may increase the effect and toxicity of lovastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
Gemfibrozil Increased risk of myopathy/rhabdomyolysis
Imatinib Imatinib, a strong CYP3A4 inhibitor, may increase the effect and toxicity of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if imatinib is initiated, discontinued or dose changed.
Indinavir Indinavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
Itraconazole Increased risk of myopathy/rhabdomyolysis
Josamycin The macrolide, josamycin, may increase the toxicity of the statin, lovastatin.
Ketoconazole Increased risk of myopathy/rhabdomyolysis
Lomitapide Lovastatin plasma concentrations may increase by lomitapide.
Nefazodone Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if nefazodone is initiated, discontinued or dose changed.
Nelfinavir Nelfinavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
Nevirapine The strong CYP3A4 inducer, nevirapine, may decrase the effect of lovastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of lovastatin if nevirapine is initiated, discontinued or dose changed.
Niacin Risk of severe myopathy/rhabdomyolysis with this combination
Quinupristin This combination presents an increased risk of toxicity
Rifabutin Rifabutin may decrease the effect of lovastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of lovastatin if rifabutin is initiated, discontinued or dose changed.
Rifampin Rifampin may decrease the effect of lovastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of lovastatin if rifampin is initiated, discontinued or dose changed.
Ritonavir Ritonavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
Saquinavir Saquinavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
Telithromycin Telithromycin may increase the adverse effects of lovastatin by decreasing its metabolism. Concomitant therapy should be avoided.
Ticagrelor Patients receiving more than 40 mg per day of lovastatin may be at increased risk of statin-related adverse effects.
Tipranavir Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Lovastatin. Concomitant therapy is contraindicated.
Verapamil Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Lovastatin by decreasing its metabolism. Avoid concurrent use if possible or reduce lovastatin dose during concomitant therapy. Monitor for changes in the therapeutic/adverse effects of Lovastatin if Verapamil is initiated, discontinued or dose changed.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if voriconazole is initiated, discontinued or dose changed.
Warfarin Lovastatin may increase the anticoagulant effect warfarin. Monitor for changes in the therapeutic and adverse effects of warfarin if lovastatin is initiated, discontinued or dose changed .
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.
Targets

1. 3-hydroxy-3-methylglutaryl-coenzyme A reductase

Pharmacological action: yes
Actions: inhibitor

This transmembrane glycoprotein is involved in the control of cholesterol biosynthesis. It is the rate-limiting enzyme of sterol biosynthesis

Organism class: human
UniProt ID: P04035 Link_out
Gene: HMGCR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. Podar K, Tai YT, Hideshima T, Vallet S, Richardson PG, Anderson KC: Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127. Pubmed
  8. Dimitroulakos J, Marhin WH, Tokunaga J, Irish J, Gullane P, Penn LZ, Kamel-Reid S: Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas. Neoplasia. 2002 Jul-Aug;4(4):337-46. Pubmed

2. Integrin alpha-L

Pharmacological action: no
Actions: other/unknown

Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. It is involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated killing, and antibody dependent killing by granulocytes and monocytes

Organism class: human
UniProt ID: P20701 Link_out
Gene: ITGAL Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kallen J, Welzenbach K, Ramage P, Geyl D, Kriwacki R, Legge G, Cottens S, Weitz-Schmidt G, Hommel U: Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain. J Mol Biol. 1999 Sep 10;292(1):1-9. Pubmed

3. Histone deacetylase 2

Pharmacological action: no
Actions: other

Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR. Interacts in the late S-phase of DNA-replication with DNMT1 in the other transcriptional repressor complex composed of DNMT1, DMAP1, PCNA, CAF1

Organism class: human
UniProt ID: Q92769 Link_out
Gene: HDAC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lin YC, Lin JH, Chou CW, Chang YF, Yeh SH, Chen CC: Statins increase p21 through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2. Cancer Res. 2008 Apr 1;68(7):2375-83. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Neuvonen PJ, Niemi M, Backman JT: Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006 Dec;80(6):565-81. Pubmed
  2. Cohen LH, van Leeuwen RE, van Thiel GC, van Pelt JF, Yap SH: Equally 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. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  5. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A5

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

3. Cytochrome P450 3A7

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

4. Serum paraoxonase/lactonase 3

Actions: substrate

Has very limited arylesterase and no paraoxonase activities but rapidly hydrolyzes lactones such as statin prodrugs (e.g. lovastatin). Hydrolyzes aromatic lactones and 5- or 6-member ring lactones with aliphatic substituents but not simple lactones or those with polar substituents (By similarity)

UniProt ID: Q15166 Link_out
Gene: PON3 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Draganov DI, Stetson PL, Watson CE, Billecke SS, La Du BN: Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation. J Biol Chem. 2000 Oct 27;275(43):33435-42. Pubmed

5. Cytochrome P450 2C8

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tornio A, Pasanen MK, Laitila J, Neuvonen PJ, Backman JT: Comparison of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as inhibitors of cytochrome P450 2C8. Basic Clin Pharmacol Toxicol. 2005 Aug;97(2):104-8. Pubmed
  2. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. Pubmed
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2C9

Actions: inhibitor, inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cohen LH, van Leeuwen RE, van Thiel GC, van Pelt JF, Yap SH: Equally 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. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 2C19

Actions: inhibitor

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cohen LH, van Leeuwen RE, van Thiel GC, van Pelt JF, Yap SH: Equally 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. Pubmed

8. Cytochrome P450 2D6

Actions: inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang E, Casciano CN, Clement RP, Johnson WW: HMG-CoA reductase inhibitors (statins) characterized as direct inhibitors of P-glycoprotein. Pharm Res. 2001 Jun;18(6):800-6. Pubmed
  2. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. Pubmed
  3. Kim RB, Wandel C, Leake B, Cvetkovic M, Fromm MF, Dempsey PJ, Roden MM, Belas F, Chaudhary AK, Roden DM, Wood AJ, Wilkinson GR: Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res. 1999 Mar;16(3):408-14. Pubmed

2. Solute carrier organic anion transporter family member 1A2

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity)

UniProt ID: P46721 Link_out
Gene: SLCO1A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. Pubmed
  2. Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP, Kirchgessner TG: A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999 Dec 24;274(52):37161-8. Pubmed

3. Solute carrier organic anion transporter family member 1B1

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver

UniProt ID: Q9Y6L6 Link_out
Gene: SLCO1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP, Kirchgessner TG: A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999 Dec 24;274(52):37161-8. Pubmed
  2. Sandhu P, Lee W, Xu X, Leake BF, Yamazaki M, Stone JA, Lin JH, Pearson PG, Kim RB: Hepatic uptake of the novel antifungal agent caspofungin. Drug Metab Dispos. 2005 May;33(5):676-82. Epub 2005 Feb 16. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19