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Identification
Name Diclofenac
Accession Number DB00586 (APRD00527)
Type small molecule
Groups approved
Description

A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Diclofenac Acid
  • Diclofenac Potassium
  • Diclofenac Sodium
  • ISV-205
Brand names
  • Allvoran
  • Apo-Diclo
  • Assaren
  • Benfofen
  • Cataflam
  • Delphimix
  • Dichlofenac
  • Dichronic
  • Diclo-Phlogont
  • Diclo-Puren
  • Diclobenin
  • Diclord
  • Dicloreum
  • Dolobasan
  • Duravolten
  • Dyloject
  • Ecofenac
  • Effekton
  • Kriplex
  • Neriodin
  • Novapirina
  • Novo-Difenac
  • Novo-Difenac SR
  • Nu-Diclo
  • Pennsaid
  • Primofenac
  • Prophenatin
  • ProSorb-D
  • Rhumalgan
  • Solaraze
  • Solaraze T
  • Tsudohmin
  • Valetan
  • Voldal
  • Voltaren
  • Voltaren Ophtha
  • Voltaren Ophthalmic
  • Voltaren Rapide
  • Voltaren SR
  • Voltaren-XR
  • Voltarol
  • Xenid
Brand name mixtures Not Available
Categories
  • Cyclooxygenase Inhibitors
  • Nonsteroidal Anti-inflammatory Agents (NSAIAs)
CAS number 15307-86-5
Weight Average: 296.149
Monoisotopic: 295.016684015
Chemical Formula C14H11Cl2NO2
InChI Key InChIKey=DCOPUUMXTXDBNB-UHFFFAOYSA-N
InChI
InChI=1S/C14H11Cl2NO2/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19/h1-7,17H,8H2,(H,18,19)
Plain Text
IUPAC Name
2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid
SMILES
OC(=O)CC1=C(NC2=C(Cl)C=CC=C2Cl)C=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Aminobenzoates
  • Phenylacetates
Substructures
  • Aminobenzoates
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Carboxylic Acids and Derivatives
  • Phenylacetates
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Aromatic compounds
  • Anilines
Pharmacology
Indication For the acute and chronic treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis.
Pharmacodynamics Diclofenac is an acetic acid nonsteroidal antiinflammatory drug (NSAID) with analgesic and antipyretic properties. Diclofenac is used to treat pain, dysmenorrhea, ocular inflammation, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and actinic keratosis
Mechanism of action The antiinflammatory effects of diclofenac are believed to be due to inhibition of both leukocyte migration and the enzyme cylooxygenase (COX-1 and COX-2), leading to the peripheral inhibition of prostaglandin synthesis. As prostaglandins sensitize pain receptors, inhibition of their synthesis is responsible for the analgesic effects of diclofenac. Antipyretic effects may be due to action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat dissipation.
Absorption Completely absorbed from the gastrointestinal tract.
Volume of distribution
  • 1.3 L/kg
Protein binding More than 99%
Metabolism

Hepatic

Enzyme Metabolite Reaction Km Vmax
Prostaglandin G/H synthase 1 3'-Hydroxydiclofenac 3'-hydroxylation
Cytochrome P450 3A4 5-Hydroxydiclofenac 5-hydroxylation
Cytochrome P450 2C9 4'-Hydroxydiclofenac 4'-hydroxylation 3.1 1.01
UDP-glucuronosyltransferase 1-1 Diclofenac acyl glucuronide glucuronidation
UDP-glucuronosyltransferase 2B7 Diclofenac acyl glucuronide glucuronidation
Route of elimination Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Little or no free unchanged diclofenac is excreted in the urine. Approximately 65% of the dose is excreted in the urine and approximately 35% in the bile as conjugates of unchanged diclofenac plus metabolites.
Half life 2 hours
Clearance
  • oral cl=622 mL/min [healthy]
  • renal cl <1 mL/min [healthy]
Toxicity Symptoms of overdose include loss of consciousness, increased intracranial pressure, and aspiration pneumonitis. LD50=390mg/kg (orally in mice)
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00093 Diclofenac Pathway SMP00093
Pharmacoeconomics
Manufacturers
  • Institut biochemique sa
  • Xanodyne pharmaceutics inc
  • Nautilus neurosciences inc
  • Novartis pharmaceuticals corp
  • Apotex inc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Nycomed us inc
  • Novartis consumer health inc
  • Akorn inc
  • Alcon inc
  • Apotex inc richmond hill
  • Bausch and lomb inc
  • Falcon pharmaceuticals ltd
  • Nexus pharmaceuticals inc
  • Mallinckrodt inc
  • Actavis elizabeth llc
  • Alphapharm party ltd
  • Carlsbad technology inc
  • Nostrum laboratories inc
  • Pliva inc
  • Roxane laboratories inc
  • Teva pharmaceuticals usa
  • Unique pharmaceutical laboratories
  • Biovail laboratories inc
  • Dexcel ltd
Packagers
Dosage forms
Form Route Strength
Solution Ophthalmic
Solution Topical
Suppository Rectal
Tablet Oral
Tablet, coated Oral
Tablet, extended release Oral
Prices
Unit description Cost Unit
Voltaren Ophtha 0.1 % Solution 2.73 USD ml
Voltaren 100 mg Suppository 1.88 USD suppository
Voltaren Sr 100 mg Sustained-Release Tablet 1.86 USD tablet
Voltaren 50 mg Suppository 1.4 USD suppository
Voltaren Sr 75 mg Sustained-Release Tablet 1.31 USD tablet
Voltaren 50 mg Enteric-Coated Tablet 0.93 USD tablet
Pms-Diclofenac 100 mg Suppository 0.88 USD suppository
Sandoz Diclofenac 100 mg Suppository 0.88 USD suppository
Novo-Difenac Sr 100 mg Sustained-Release Tablet 0.8 USD tablet
Pms-Diclofenac-Sr 100 mg Sustained-Release Tablet 0.8 USD tablet
Sandoz Diclofenac Sr 100 mg Sustained-Release Tablet 0.8 USD tablet
Pms-Diclofenac 50 mg Suppository 0.65 USD suppository
Sandoz Diclofenac 50 mg Suppository 0.65 USD suppository
Novo-Difenac Sr 75 mg Sustained-Release Tablet 0.6 USD tablet
Pms-Diclofenac-Sr 75 mg Sustained-Release Tablet 0.6 USD tablet
Sandoz Diclofenac Sr 75 mg Sustained-Release Tablet 0.6 USD tablet
Apo-Diclo 50 mg Enteric-Coated Tablet 0.4 USD tablet
Novo-Difenac 50 mg Enteric-Coated Tablet 0.4 USD tablet
Pms-Diclofenac 50 mg Enteric-Coated Tablet 0.4 USD tablet
Sandoz Diclofenac 50 mg Enteric-Coated Tablet 0.4 USD tablet
Apo-Diclo 25 mg Enteric-Coated Tablet 0.2 USD tablet
Novo-Difenac 25 mg Enteric-Coated Tablet 0.2 USD tablet
Nu-Diclo 25 mg Enteric-Coated Tablet 0.2 USD tablet
Pms-Diclofenac 25 mg Enteric-Coated Tablet 0.2 USD tablet
Sandoz Diclofenac 25 mg Enteric-Coated Tablet 0.2 USD tablet
Patents
Country Patent Number Approved Expires
United States 7662858 2009-02-24 2029-02-24
United States 5607690 1994-04-13 2014-04-13
Properties
State solid
Melting point 283-285oC
Experimental Properties
Property Value Source
water solubility 50 mg/mL (sodium salt) [Sigma Aldrich] PhysProp
logP 3.9 PhysProp
pKa 4.15 Various sources
Predicted Properties
Property Value Source
water solubility 4.47e-03 g/l ALOGPS
logP 4.98 ALOGPS
logP 4.26 ChemAxon Molconvert
logS -4.82 ALOGPS
pKa 16.40 ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 49.33 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 75.46 ChemAxon Molconvert
polarizability 27.93 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C: Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006 Jun 3;332(7553):1302-8. Pubmed
  2. Solomon DH, Avorn J, Sturmer T, Glynn RJ, Mogun H, Schneeweiss S: Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: high-risk subgroups and time course of risk. Arthritis Rheum. 2006 May;54(5):1378-89. Pubmed
  3. FitzGerald GA, Patrono C: The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med. 2001 Aug 9;345(6):433-42. Pubmed
  4. Graham DJ: COX-2 inhibitors, other NSAIDs, and cardiovascular risk: the seduction of common sense. JAMA. 2006 Oct 4;296(13):1653-6. Epub 2006 Sep 12. Pubmed
  5. Brater DC: Renal effects of cyclooxygyenase-2-selective inhibitors. J Pain Symptom Manage. 2002 Apr;23(4 Suppl):S15-20; discussion S21-3. Pubmed
  6. Sigma Aldrich Link
  7. Gan TJ: Diclofenac: an update on its mechanism of action and safety profile. Curr Med Res Opin. 2010 Jul;26(7):1715-31. Pubmed
External Links
Resource Link
KEGG Compound C01690 Link_out
PubChem Compound 3033 Link_out
PubChem Substance 46504644 Link_out
ChemSpider 2925 Link_out
BindingDB 13066 Link_out
ChEBI 4507 Link_out
ChEMBL 4507 Link_out
Therapeutic Targets Database DAP000620 Link_out
PharmGKB PA449293 Link_out
HET DIF Link_out
Drug Product Database 2241225 Link_out
RxList http://www.rxlist.com/cgi/generic/diclofen.htm Link_out
Drugs.com http://www.drugs.com/cdi/diclofenac-drops.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Diclofenac Link_out
ATC Codes
  • M01AB05
  • M02AA15
  • S01BC03
  • D11AX18
AHFS Codes
  • 28:08.04.92
  • 28:08.04.08
PDB Entries Not Available
FDA label show (37.5 KB)
MSDS show (73.6 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation.
Targets

1. Prostaglandin G/H synthase 2

Pharmacological action: yes
Actions: inhibitor

May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity

Organism class: human
UniProt ID: P35354 Link_out
Gene: PTGS2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kirchheiner J, Meineke I, Steinbach N, Meisel C, Roots I, Brockmoller J: Pharmacokinetics of diclofenac and inhibition of cyclooxygenases 1 and 2: no relationship to the CYP2C9 genetic polymorphism in humans. Br J Clin Pharmacol. 2003 Jan;55(1):51-61. Pubmed
  2. Blomme EA, Chinn KS, Hardy MM, Casler JJ, Kim SH, Opsahl AC, Hall WA, Trajkovic D, Khan KN, Tripp CS: Selective cyclooxygenase-2 inhibition does not affect the healing of cutaneous full-thickness incisional wounds in SKH-1 mice. Br J Dermatol. 2003 Feb;148(2):211-23. Pubmed
  3. Beubler E: [Pharmacology of cyclooxygenase 2 inhibition] Wien Med Wochenschr. 2003;153(5-6):95-9. Pubmed
  4. Chavez ML, DeKorte CJ: Valdecoxib: a review. Clin Ther. 2003 Mar;25(3):817-51. Pubmed
  5. Rowlinson SW, Kiefer JR, Prusakiewicz JJ, Pawlitz JL, Kozak KR, Kalgutkar AS, Stallings WC, Kurumbail RG, Marnett LJ: A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385. J Biol Chem. 2003 Nov 14;278(46):45763-9. Epub 2003 Aug 18. Pubmed

2. Prostaglandin G/H synthase 1

Pharmacological action: yes
Actions: inhibitor

May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells

Organism class: human
UniProt ID: P23219 Link_out
Gene: PTGS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Calkin AC, Sudhir K, Honisett S, Williams MR, Dawood T, Komesaroff PA: Rapid potentiation of endothelium-dependent vasodilation by estradiol in postmenopausal women is mediated via cyclooxygenase 2. J Clin Endocrinol Metab. 2002 Nov;87(11):5072-5. Pubmed
  2. Kirchheiner J, Meineke I, Steinbach N, Meisel C, Roots I, Brockmoller J: Pharmacokinetics of diclofenac and inhibition of cyclooxygenases 1 and 2: no relationship to the CYP2C9 genetic polymorphism in humans. Br J Clin Pharmacol. 2003 Jan;55(1):51-61. Pubmed
  3. Kampfer H, Brautigam L, Geisslinger G, Pfeilschifter J, Frank S: Cyclooxygenase-1-coupled prostaglandin biosynthesis constitutes an essential prerequisite for skin repair. J Invest Dermatol. 2003 May;120(5):880-90. Pubmed
  4. Chavez ML, DeKorte CJ: Valdecoxib: a review. Clin Ther. 2003 Mar;25(3):817-51. Pubmed
  5. Hinz B, Rau T, Auge D, Werner U, Ramer R, Rietbrock S, Brune K: Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac. Clin Pharmacol Ther. 2003 Sep;74(3):222-35. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Arachidonate 5-lipoxygenase

Pharmacological action: yes
Actions: potentiator
Organism class: human
UniProt ID: P09917 Link_out
Gene: ALOX5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Charlier C, Michaux C: Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs. Eur J Med Chem. 2003 Jul-Aug;38(7-8):645-59. Pubmed
  2. Kudo C, Kori M, Matsuzaki K, Yamai K, Nakajima A, Shibuya A, Niwa H, Kamisaki Y, Wada K: Diclofenac inhibits proliferation and differentiation of neural stem cells. Biochem Pharmacol. 2003 Jul 15;66(2):289-95. Pubmed
  3. Whittle BJ: Cyclooxygenase and nitric oxide systems in the gut as therapeutic targets for safer anti-inflammatory drugs. Curr Opin Pharmacol. 2004 Dec;4(6):538-45. Pubmed

4. Sodium channel protein type 4 subunit alpha

Pharmacological action: yes
Actions: inhibitor

This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle

Organism class: human
UniProt ID: P35499 Link_out
Gene: SCN4A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yang YC, Kuo CC: An inactivation stabilizer of the Na+ channel acts as an opportunistic pore blocker modulated by external Na+. J Gen Physiol. 2005 May;125(5):465-81. Epub 2005 Apr 11. Pubmed
  2. Voilley N: Acid-sensing ion channels (ASICs): new targets for the analgesic effects of non-steroid anti-inflammatory drugs (NSAIDs). Curr Drug Targets Inflamm Allergy. 2004 Mar;3(1):71-9. Pubmed
  3. Jones NG, Slater R, Cadiou H, McNaughton P, McMahon SB: Acid-induced pain and its modulation in humans. J Neurosci. 2004 Dec 1;24(48):10974-9. Pubmed

5. Amiloride-sensitive cation channel 2, neuronal

Pharmacological action: yes
Actions: inhibitor

Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Also permeable for Ca(2+), Li(+) and K(+). Generates a biphasic current with a fast inactivating and a slow sustained phase. Mediates glutamate-independent Ca(2+) entry into neurons upon acidosis. This Ca(2+) overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties

Organism class: human
UniProt ID: P78348 Link_out
Gene: ACCN2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Voilley N, de Weille J, Mamet J, Lazdunski M: Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J Neurosci. 2001 Oct 15;21(20):8026-33. Pubmed

6. Potassium voltage-gated channel subfamily KQT member 2

Pharmacological action: yes
Actions: other

Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. KCNQ2/KCNQ3 current is blocked by linopirdine and XE991, and activated by the anticonvulsant retigabine. Muscarinic agonist oxotremorine-M strongly suppress KCNQ2/KCNQ3 current in cells in which cloned KCNQ2/KCNQ3 channels were coexpressed with M1 muscarinic receptors

Organism class: human
UniProt ID: O43526 Link_out
Gene: KCNQ2 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Peretz A, Degani N, Nachman R, Uziyel Y, Gibor G, Shabat D, Attali B: Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties. Mol Pharmacol. 2005 Apr;67(4):1053-66. Epub 2004 Dec 14. Pubmed
  2. Xiong Q, Gao Z, Wang W, Li M: Activation of Kv7 (KCNQ) voltage-gated potassium channels by synthetic compounds. Trends Pharmacol Sci. 2008 Feb;29(2):99-107. Epub 2008 Jan 18. Pubmed

7. Potassium voltage-gated channel subfamily KQT member 3

Pharmacological action: yes
Actions: other

Probably important in the regulation of neuronal excitability. Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs

Organism class: human
UniProt ID: O43525 Link_out
Gene: KCNQ3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Xiong Q, Gao Z, Wang W, Li M: Activation of Kv7 (KCNQ) voltage-gated potassium channels by synthetic compounds. Trends Pharmacol Sci. 2008 Feb;29(2):99-107. Epub 2008 Jan 18. Pubmed
  2. Peretz A, Degani N, Nachman R, Uziyel Y, Gibor G, Shabat D, Attali B: Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties. Mol Pharmacol. 2005 Apr;67(4):1053-66. Epub 2004 Dec 14. Pubmed

8. Phospholipase A2, membrane associated

Pharmacological action: unknown
Actions: inhibitor

Thought to participate in the regulation of the phospholipid metabolism in biomembranes including eicosanoid biosynthesis. Catalyzes the calcium-dependent hydrolysis of the 2- acyl groups in 3-sn-phosphoglycerides

Organism class: human
UniProt ID: P14555 Link_out
Gene: PLA2G2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Madanick RD, O’Loughlin CJ, Barkin JS: Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography. Dig Dis Sci. 2005 May;50(5):879-81. Pubmed
  2. Singh N, Jabeen T, Sharma S, Somvanshi RK, Dey S, Srinivasan A, Singh TP: Specific binding of non-steroidal anti-inflammatory drugs (NSAIDs) to phospholipase A2: structure of the complex formed between phospholipase A2 and diclofenac at 2.7 A resolution. Acta Crystallogr D Biol Crystallogr. 2006 Apr;62(Pt 4):410-6. Epub 2006 Mar 18. Pubmed
  3. Makela A, Kuusi T, Schroder T: Inhibition of serum phospholipase-A2 in acute pancreatitis by pharmacological agents in vitro. Scand J Clin Lab Invest. 1997 Aug;57(5):401-7. Pubmed
Enzymes

1. Cytochrome P450 2C9

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 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. Mo SL, Zhou ZW, Yang LP, Wei MQ, Zhou SF: New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126. Pubmed
  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. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. 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
  5. Obach RS, Reed-Hagen AE: Measurement of Michaelis constants for cytochrome P450-mediated biotransformation reactions using a substrate depletion approach. Drug Metab Dispos. 2002 Jul;30(7):831-7. Pubmed
  6. Leemann T, Transon C, Dayer P: Cytochrome P450TB (CYP2C): a major monooxygenase catalyzing diclofenac 4’-hydroxylation in human liver. Life Sci. 1993;52(1):29-34. Pubmed

2. Cytochrome P450 2C19

Actions: substrate

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. 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

3. Cytochrome P450 1A2

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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
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

4. Cytochrome P450 2C8

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. 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. 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

5. UDP-glucuronosyltransferase 1-1

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX- alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate

UniProt ID: P22309 Link_out
Gene: UGT1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

6. UDP-glucuronosyltransferase 2B7

Actions: substrate

Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites

UniProt ID: P16662 Link_out
Gene: UGT2B7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

7. Prostaglandin G/H synthase 1

Actions: substrate

May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells

UniProt ID: P23219 Link_out
Gene: PTGS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

8. Cytochrome P450 3A4

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 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. 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
  2. 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

9. Cytochrome P450 1A1

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: P04798 Link_out
Gene: CYP1A1 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

10. Cytochrome P450 2B6

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: P20813 Link_out
Gene: CYP2B6 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

11. Cytochrome P450 2C18

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: P33260 Link_out
Gene: CYP2C18 Link_out
Protein 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

12. Cytochrome P450 2E1

Actions: inhibitor

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 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-associated protein 4

Actions: inhibitor

May be an organic anion pump relevant to cellular detoxification

UniProt ID: O15439 Link_out
Gene: ABCC4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9. Epub 2003 Jun 30. Pubmed

2. 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, Lew K, Barecki M, Casciano CN, Clement RP, Johnson WW: Quantitative distinctions of active site molecular recognition by P-glycoprotein and cytochrome P450 3A4. Chem Res Toxicol. 2001 Dec;14(12):1596-603. Pubmed

3. Multidrug resistance-associated protein 1

Actions: inhibitor

May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Confers resistance to anticancer drugs. Transports LTC4. May protect milk against xenobiotics

UniProt ID: P33527 Link_out
Gene: ABCC1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9. Epub 2003 Jun 30. Pubmed

4. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mulato AS, Ho ES, Cihlar T: Nonsteroidal anti-inflammatory drugs efficiently reduce the transport and cytotoxicity of adefovir mediated by the human renal organic anion transporter 1. J Pharmacol Exp Ther. 2000 Oct;295(1):10-5. Pubmed
  2. Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G: Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519-24. Pubmed
  3. Apiwattanakul N, Sekine T, Chairoungdua A, Kanai Y, Nakajima N, Sophasan S, Endou H: Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes. Mol Pharmacol. 1999 May;55(5):847-54. Pubmed

5. Solute carrier family 22 member 8

Actions: inhibitor

Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone- 3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA)

UniProt ID: Q8TCC7 Link_out
Gene: SLC22A8 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. Pubmed

6. Solute carrier organic anion transporter family member 1C1

Actions: inhibitor

Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones thyroxine (T4) and rT3. Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol, estrone-3-sulfate and sulfobromophthalein (BSP) are transported with much lower efficiency

UniProt ID: Q9NYB5 Link_out
Gene: SLCO1C1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Westholm DE, Stenehjem DD, Rumbley JN, Drewes LR, Anderson GW: Competitive inhibition of organic anion transporting polypeptide 1c1-mediated thyroxine transport by the fenamate class of nonsteroidal antiinflammatory drugs. Endocrinology. 2009 Feb;150(2):1025-32. Epub 2008 Oct 9. Pubmed
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

7. Solute carrier family 22 member 11

Actions: inhibitor

Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds

UniProt ID: Q9NSA0 Link_out
Gene: SLC22A11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cha SH, Sekine T, Kusuhara H, Yu E, Kim JY, Kim DK, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta. J Biol Chem. 2000 Feb 11;275(6):4507-12. Pubmed
Carriers

1. Transthyretin

Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain

UniProt ID: P02766 Link_out
Gene: TTR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Miller SR, Sekijima Y, Kelly JW: Native state stabilization by NSAIDs inhibits transthyretin amyloidogenesis from the most common familial disease variants. Lab Invest. 2004 May;84(5):545-52. Pubmed
  2. Almeida MR, Macedo B, Cardoso I, Alves I, Valencia G, Arsequell G, Planas A, Saraiva MJ: Selective binding to transthyretin and tetramer stabilization in serum from patients with familial amyloidotic polyneuropathy by an iodinated diflunisal derivative. Biochem J. 2004 Jul 15;381(Pt 2):351-6. Pubmed

2. Serum albumin

Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood

UniProt ID: P02768 Link_out
Gene: ALB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yamasaki K, Rahman MH, Tsutsumi Y, Maruyama T, Ahmed S, Kragh-Hansen U, Otagiri M: Circular dichroism simulation shows a site-II-to-site-I displacement of human serum albumin-bound diclofenac by ibuprofen. AAPS PharmSciTech. 2000 May 14;1(2):E12. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on July 22, 2011 07:52

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.