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Identification
Name Sulindac
Accession Number DB00605 (APRD01243)
Type small molecule
Groups approved
Description

Sulindac is a nonsteroidal anti-inflammatory agent (NSAIA) of the arylalkanoic acid class that is marketed in the U.S. by Merck as Clinoril. Like other NSAIAs, it may be used in the treatment of acute or chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene, that is converted in vivo to an active sulfide compound by liver enzymes. The sulfide metabolite then undergoes enterohepatic circulation; it is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAIA’s except for drugs of the cyclooxygenase-2 (COX-2) inhibitor class. The exact mechanism of its NSAIA properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting prostaglandin synthesis.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Clinoril Merck
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Anti-inflammatory Agents
  • Cyclooxygenase Inhibitors
  • Analgesics
  • Analgesics, Non-Narcotic
  • Antipyretics
  • Nonsteroidal Anti-inflammatory Agents (NSAIAs)
CAS number 38194-50-2
Weight Average: 356.411
Monoisotopic: 356.088243305
Chemical Formula C20H17FO3S
InChI Key InChIKey=MLKXDPUZXIRXEP-MFOYZWKCSA-N
InChI
InChI=1S/C20H17FO3S/c1-12-17(9-13-3-6-15(7-4-13)25(2)24)16-8-5-14(21)10-19(16)18(12)11-20(22)23/h3-10H,11H2,1-2H3,(H,22,23)/b17-9-
Plain Text
IUPAC Name
2-[(1Z)-5-fluoro-1-[(4-methanesulfinylphenyl)methylidene]-2-methyl-1H-inden-3-yl]acetic acid
SMILES
CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(C=C1)S(C)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For acute or long-term use in the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute painful shoulder (acute subacromial bursitis/supraspinatus tendinitis), and acute gouty arthritis.
Pharmacodynamics Sulindac is a non-steroidal anti-inflammatory indene derivative, also possessing analgesic and antipyretic activities.
Mechanism of action Sulindac's exact mechanism of action is unknown. Its antiinflammatory effects are believed to be due to inhibition of both COX-1 and COX-2 which leads to the inhibition of prostaglandin synthesis. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.
Absorption Approximately 90% absorbed in humans following oral administration.
Volume of distribution Not Available
Protein binding At 1 mcg/ml concentrations, approximately 93% sulindac and 98% of its sulfide metabolite are bound to human serum albumin.
Metabolism
Undergoes two major biotransformations: reversible reduction to the sulfide metabolite, and irreversible oxidation to the sulfone metabolite. Sulindac and its sulfide and sulfone metabolites undergo extensive enterohepatic circulation. Available evidence indicates that the biological activity resides with the sulfide metabolite. Side chain hydroxylation and hydration of the double bond also occur.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Sulindac
    		Sulindac sulfide Details
    Sulindac
      		Sulindac sulfone Details
      Route of elimination Sulindac is excreted in rat milk; concentrations in milk were 10 to 20% of those levels in plasma. It is not known if sulindac is excreted in human milk. Approximately 50% of the administered dose of sulindac is excreted in the urine with the conjugated sulfone metabolite accounting for the major portion. Hepatic metabolism is an important elimination pathway.
      Half life The mean half-life of sulindac is 7.8 hours while the mean half-life of the sulfide metabolite is 16.4 hours.
      Clearance
      • Renal cl=68.12 +/- 27.56 mL/min [NORMAL (19-41 yrs)]
      Toxicity Acute oral toxicity (LD50) in rats is 264 mg/kg. Cases of overdose have been reported and rarely, deaths have occurred. The following signs and symptoms may be observed following overdose: stupor, coma, diminished urine output and hypotension.
      Affected organisms
      • Humans and other mammals
      Pathways
      Pathway Name SMPDB ID
      Smp00094 Sulindac Pathway SMP00094
      Pharmacoeconomics
      Manufacturers
      • Merck research laboratories div merck co inc
      • Epic pharma llc
      • Heritage pharmaceuticals inc
      • Mutual pharmaceutical co inc
      • Mylan pharmaceuticals inc
      • Sandoz inc
      • Teva pharmaceuticals usa inc
      • Watson laboratories inc
      Packagers
      Dosage forms
      Form Route Strength
      Tablet Oral 150 mg
      Tablet Oral 200 mg
      Prices
      Unit description Cost Unit
      Sulindac powder 17.36 USD g
      Clinoril 200 mg tablet 1.58 USD tablet
      Sulindac 200 mg tablet 1.23 USD tablet
      Sulindac 150 mg tablet 1.0 USD tablet
      Apo-Sulin 200 mg Tablet 0.51 USD tablet
      Novo-Sundac 200 mg Tablet 0.51 USD tablet
      Nu-Sulindac 200 mg Tablet 0.51 USD tablet
      Apo-Sulin 150 mg Tablet 0.4 USD tablet
      Novo-Sundac 150 mg Tablet 0.4 USD tablet
      Nu-Sulindac 150 mg Tablet 0.4 USD tablet
      DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
      Patents Not Available
      Properties
      State solid
      Experimental Properties
      Property Value Source
      melting point 183 °C PhysProp
      water solubility 3000 mg/L MERCK INDEX (1996); pH 7
      logP 3.42 SANGSTER (1993)
      pKa 4.7 MERCK INDEX (1996)
      Predicted Properties
      Property Value Source
      water solubility 2.51e-02 g/l ALOGPS
      logP 2.96 ALOGPS
      logP 2.93 ChemAxon
      logS -4.2 ALOGPS
      pKa (strongest acidic) 4.09 ChemAxon
      pKa (strongest basic) -6.7 ChemAxon
      physiological charge -1 ChemAxon
      hydrogen acceptor count 3 ChemAxon
      hydrogen donor count 1 ChemAxon
      polar surface area 54.37 ChemAxon
      rotatable bond count 4 ChemAxon
      refractivity 99.56 ChemAxon
      polarizability 37.2 ChemAxon
      References
      Synthesis Reference Not Available
      General Reference Not Available
      External Links
      Resource Link
      KEGG Drug D00120 Link_out
      KEGG Compound C01531 Link_out
      ChEBI 9352 Link_out
      ChEMBL 9352 Link_out
      Therapeutic Targets Database DAP000569 Link_out
      PharmGKB PA451565 Link_out
      Drug Product Database 808636 Link_out
      RxList http://www.rxlist.com/cgi/generic3/sulindac.htm Link_out
      Drugs.com http://www.drugs.com/cdi/sulindac.html Link_out
      PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cli1087.shtml Link_out
      Wikipedia http://en.wikipedia.org/wiki/Sulindac Link_out
      ATC Codes
      • M01AB02
      AHFS Codes
      • 28:08.04.92
      PDB Entries Not Available
      FDA label show (106 KB)
      MSDS show (73.2 KB)
      Interactions
      Drug Interactions
      Drug Interaction
      Acenocoumarol The NSAID, sulindac, may increase the anticoagulant effect of acenocoumarol. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.
      Acetylsalicylic acid Risk of additive toxicity (e.g. bleed risk). Acetylsalicylic acid may decrease the serum concentration of sulindac. Sulindac may counteract the cardioprotective effects of acetylsalicylic acid. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if the interacting agent is initiated, discontinued or dose changed.
      Aminosalicylic Acid Risk of additive toxicity (e.g. bleed risk). Aminosalicylic acid may decrease the serum concentration of sulindac. Consider alternate therapy or monitor for changes in the therapeutic effects of sulindac and adverse effects of both agents if the interacting agent is initiated, discontinued or dose changed.
      Azilsartan medoxomil Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
      Bumetanide The NSAID, sulindac, decreases the diuretic and antihypertensive effects of the loop diuretic, bumetanide.
      Cholestyramine The bile acid sequestrant, cholestyramine, may decrease the absorption of the NSAID, sulindac. Monitor for changes in the therapeutic and adverse effects of sulindac if cholestyramine is initiated, discontinued or dose changed. Administering the two agents 2 or more hours apart may reduce, but not eliminate, the risk of this interactions.
      Colesevelam The bile acid sequestrant, colesevelam, may decrease the absorption of the NSAID, sulindac. Sulindac should be administered at least 1 hour before or 4 hours after colesevelam. Monitor for changes in the therapeutic and adverse effects of sulindac if colesevelam is initiated, discontinued or dose changed.
      Colestipol The bile acid sequestrant, colestipol, may decrease the absorption of the NSAID, sulindac. Monitor for changes in the therapeutic and adverse effects of sulindac if colestipol is initiated, discontinued or dose changed. Administering the two agents 2 or more hours apart may reduce, but not eliminate, the risk of this interactions.
      Cyclosporine The NSAID, sulindac, may increase the nephrotoxic effect of cyclosporine. Sulindac may increase the serum concentration of cyclosporine. Consider alternate therapy or monitor for increased cyclosporine levels and nephrotoxicity during concomitant therapy.
      Ethacrynic acid The NSAID, sulindac, may decrease the diuretic and antihypertensive effects of the loop diuretic, ethacryninc acid.
      Furosemide The NSAID, sulindac, may decrease the diuretic and antihypertensive effects of the loop diuretic, furosemide.
      Ginkgo biloba Ginkgo biloba may enhance the anticoagulant effect of sulindac. Increased risk of bleeding, bruising and altered mental status due to CNS bleeds. Concomitant therapy should be avoided.
      Ginseng Ginseng may enhance the anticoagulant effect of sulindac. Increased risk of bleeding, bruising and altered mental status due to CNS bleeds. Concomitant therapy should be avoided.
      Ketorolac May cause additive or synergistic NSAID toxicities (e.g. GI bleeding, renal dysfunction, etc.). Concomitant therapy is contraindicated.
      Methotrexate The NSAID, sulindac, may decrease the clearance methotrexate. Consider alternate therapy, especially in patients receiving high antineoplastic doses of methotrexate. Otherwise, monitor for hematologic and renal toxicities.
      Pemetrexed The NSAID, sulindac, may increase the serum concentration of pemetrexed by decreasing its elimination. This interaction more prevalent in patients with mild to moderate renal insufficiency. Consider alternate therapy or monitor for pemetrexed toxicity during concomitant therapy.
      Pralatrexate NSAIDs increase the risk of toxicity due to impairment of renal clearance of pralatrexate thus increasing exposure. Monitor for adverse effects or adjust dose of pralatrexate.
      S-Adenosylmethionine S-adenosylmethionine may enhance the anticoagulant effect of sulindac. Increased risk of bleeding, bruising and altered mental status due to CNS bleeds. Concomitant therapy should be avoided.
      Salicylate-sodium Risk of additive toxicity (e.g. bleed risk). Salicylate-sodium may decrease the serum concentration of sulindac. Consider alternate therapy or monitor for changes in the therapeutic effects of sulindac and adverse effects of both agents if the interacting agent is initiated, discontinued or dose changed.
      Salsalate Risk of additive toxicity (e.g. bleed risk). Salsalate may decrease the serum concentration of sulindac. Consider alternate therapy or monitor for changes in the therapeutic effects of sulindac and adverse effects of both agents if the interacting agent is initiated, discontinued or dose changed.
      Telmisartan Concomitant use of Telmisartan and Sulindac may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
      Timolol The NSAID, Sulindac, may antagonize the antihypertensive effect of Timolol.
      Trandolapril The NSAID, Sulindac, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Sulindac is initiated, discontinued or dose changed.
      Treprostinil The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Sulindac. Monitor for increased bleeding during concomitant thearpy.
      Warfarin The antiplatelet effects of sulindac may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.
      Food Interactions Not Available
      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. Giuliano F, Warner TD: Ex vivo assay to determine the cyclooxygenase selectivity of non-steroidal anti-inflammatory drugs. Br J Pharmacol. 1999 Apr;126(8):1824-30. Pubmed
      2. Molina MA, Sitja-Arnau M, Lemoine MG, Frazier ML, Sinicrope FA: Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs. Cancer Res. 1999 Sep 1;59(17):4356-62. Pubmed
      3. Yip-Schneider MT, Barnard DS, Billings SD, Cheng L, Heilman DK, Lin A, Marshall SJ, Crowell PL, Marshall MS, Sweeney CJ: Cyclooxygenase-2 expression in human pancreatic adenocarcinomas. Carcinogenesis. 2000 Feb;21(2):139-46. Pubmed
      4. Fosslien E: Biochemistry of cyclooxygenase (COX)-2 inhibitors and molecular pathology of COX-2 in neoplasia. Crit Rev Clin Lab Sci. 2000 Oct;37(5):431-502. Pubmed
      5. Taylor MT, Lawson KR, Ignatenko NA, Marek SE, Stringer DE, Skovan BA, Gerner EW: Sulindac sulfone inhibits K-ras-dependent cyclooxygenase-2 expression in human colon cancer cells. Cancer Res. 2000 Dec 1;60(23):6607-10. Pubmed

      2. Prostaglandin G/H synthase 1

      Pharmacological action: unknown
      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. Giuliano F, Warner TD: Ex vivo assay to determine the cyclooxygenase selectivity of non-steroidal anti-inflammatory drugs. Br J Pharmacol. 1999 Apr;126(8):1824-30. Pubmed
      2. Lim JT, Piazza GA, Han EK, Delohery TM, Li H, Finn TS, Buttyan R, Yamamoto H, Sperl GJ, Brendel K, Gross PH, Pamukcu R, Weinstein IB: Sulindac derivatives inhibit growth and induce apoptosis in human prostate cancer cell lines. Biochem Pharmacol. 1999 Oct 1;58(7):1097-107. Pubmed
      3. Soriano AF, Helfrich B, Chan DC, Heasley LE, Bunn PA Jr, Chou TC: Synergistic effects of new chemopreventive agents and conventional cytotoxic agents against human lung cancer cell lines. Cancer Res. 1999 Dec 15;59(24):6178-84. Pubmed
      4. Cheng ZJ, Tikkanen I, Vapaatalo H, Mervaala EM: Vascular effects of COX inhibition and AT1 receptor blockade in transgenic rats harboring mouse renin-2 gene. J Physiol Pharmacol. 2002 Dec;53(4 Pt 1):597-613. Pubmed
      5. Cheng ZJ, Finckenberg P, Louhelainen M, Merasto S, Tikkanen I, Vapaatalo H, Mervaala EM: Cardiovascular and renal effects of cyclooxygenase inhibition in transgenic rats harboring mouse renin-2 gene (TGR[mREN2]27). Eur J Pharmacol. 2003 Feb 14;461(2-3):159-69. Pubmed

      3. Aldose reductase

      Pharmacological action: unknown
      Actions: inhibitor

      Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies

      Organism class: human
      UniProt ID: P15121 Link_out
      Gene: AKR1B1 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Sharma YR, Vajpayee RB, Bhatnagar R, Mohan M, Azad RV, Kumar M, Nath R: Topical sulindac therapy in diabetic senile cataracts: cataract-IV. Indian J Ophthalmol. 1989 Jul-Sep;37(3):127-33. Pubmed
      2. Crabbe MJ, Freeman G, Halder AB, Bron AJ: The inhibition of bovine lens aldose reductase by Clinoril, its absorption into the human red cell and its effect on human red cell aldose reductase activity. Ophthalmic Res. 1985;17(2):85-9. Pubmed
      3. Chaudhry PS, Cabrera J, Juliani HR, Varma SD: Inhibition of human lens aldose reductase by flavonoids, sulindac and indomethacin. Biochem Pharmacol. 1983 Jul 1;32(13):1995-8. Pubmed
      4. Jacobson M, Sharma YR, Cotlier E, Hollander JD: Diabetic complications in lens and nerve and their prevention by sulindac or sorbinil: two novel aldose reductase inhibitors. Invest Ophthalmol Vis Sci. 1983 Oct;24(10):1426-9. Pubmed
      5. van der Sloot P, Mizisin A, Zochodne D: Sulindac in established experimental diabetes: a follow-up study. Can J Neurol Sci. 1995 Aug;22(3):198-201. Pubmed
      6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

      4. Mitogen-activated protein kinase 3

      Pharmacological action: unknown
      Actions: inhibitor

      Involved in both the initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors such as ELK-1. Phosphorylates EIF4EBP1; required for initiation of translation. Phosphorylates microtubule-associated protein 2 (MAP2). Phosphorylates SPZ1

      Organism class: human
      UniProt ID: P27361 Link_out
      Gene: MAPK3 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Rice PL, Goldberg RJ, Ray EC, Driggers LJ, Ahnen DJ: Inhibition of extracellular signal-regulated kinase 1/2 phosphorylation and induction of apoptosis by sulindac metabolites. Cancer Res. 2001 Feb 15;61(4):1541-7. Pubmed
      2. Rice PL, Washington M, Schleman S, Beard KS, Driggers LJ, Ahnen DJ: Sulindac sulfide inhibits epidermal growth factor-induced phosphorylation of extracellular-regulated kinase 1/2 and Bad in human colon cancer cells. Cancer Res. 2003 Feb 1;63(3):616-20. Pubmed
      3. Rice PL, Beard KS, Driggers LJ, Ahnen DJ: Inhibition of extracellular-signal regulated kinases 1/2 is required for apoptosis of human colon cancer cells in vitro by sulindac metabolites. Cancer Res. 2004 Nov 15;64(22):8148-51. Pubmed
      4. Pangburn HA, Kraus H, Ahnen DJ, Rice PL: Sulindac metabolites inhibit epidermal growth factor receptor activation and expression. J Carcinog. 2005 Sep 2;4:16. Pubmed
      5. Rice PL, Peters SL, Beard KS, Ahnen DJ: Sulindac independently modulates extracellular signal-regulated kinase 1/2 and cyclic GMP-dependent protein kinase signaling pathways. Mol Cancer Ther. 2006 Mar;5(3):746-54. Pubmed

      5. Peroxisome proliferator-activated receptor delta

      Pharmacological action: unknown
      Actions: negative modulator

      Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Decreases expression of NPC1L1 once activated by a ligand

      Organism class: human
      UniProt ID: Q03181 Link_out
      Gene: PPARD Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. He TC, Chan TA, Vogelstein B, Kinzler KW: PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell. 1999 Oct 29;99(3):335-45. Pubmed
      2. Babbar N, Ignatenko NA, Casero RA Jr, Gerner EW: Cyclooxygenase-independent induction of apoptosis by sulindac sulfone is mediated by polyamines in colon cancer. J Biol Chem. 2003 Nov 28;278(48):47762-75. Epub 2003 Sep 23. Pubmed
      3. Jarvis MC, Gray TJ, Palmer CN: Both PPARgamma and PPARdelta influence sulindac sulfide-mediated p21WAF1/CIP1 upregulation in a human prostate epithelial cell line. Oncogene. 2005 Dec 8;24(55):8211-5. Pubmed
      4. Kim DJ, Prabhu KS, Gonzalez FJ, Peters JM: Inhibition of chemically induced skin carcinogenesis by sulindac is independent of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta). Carcinogenesis. 2006 May;27(5):1105-12. Epub 2006 Jan 16. Pubmed
      5. Liou JY, Ghelani D, Yeh S, Wu KK: Nonsteroidal anti-inflammatory drugs induce colorectal cancer cell apoptosis by suppressing 14-3-3epsilon. Cancer Res. 2007 Apr 1;67(7):3185-91. Pubmed

      6. Putative G-protein coupled receptor 44

      Pharmacological action: unknown
      Actions: antagonist

      Orphan receptor

      Organism class: human
      UniProt ID: Q9Y5Y4 Link_out
      Gene: GPR44 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Hata AN, Lybrand TP, Marnett LJ, Breyer RM: Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2. Mol Pharmacol. 2005 Mar;67(3):640-7. Epub 2004 Nov 24. Pubmed
      Enzymes

      1. Cytochrome P450 1A1

      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

      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

      2. Cytochrome P450 1A2

      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. 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
      Transporters

      1. 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. 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
      Carriers

      1. 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. Russeva VN, Zhivkova ZD: Molecular basis of sulindac competition with specific markers for the major binding sites on human serum albumin. Arzneimittelforschung. 2003;53(3):174-81. Pubmed
      2. Shams-Eldeen MA, Vallner JJ, Needham TE: Interaction of sulindac and metabolite with human serum albumin. J Pharm Sci. 1978 Aug;67(8):1077-80. Pubmed
      3. Zhivkova ZD, Russeva VN: Thermodynamic characterization of the binding process of sulindac to human serum albumin. Arzneimittelforschung. 2003;53(1):53-6. Pubmed
      Comments
      Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19