Resource Sitaxentan

Predicate	Value (sorted: default)
rdfs:label	"Sitaxentan"
rdf:type	drugbank:drugs
drugbank:description	" 210421-64-0 approved investigational Investigated for use/treatment in pulmonary hypertension, connective tissue diseases, hypertension, and congestive heart failure. Sitaxentan belongs to a class of drugs known as endothelin receptor antagonists (ERAs). Patients with PAH have elevated levels of endothelin, a potent blood vessel constrictor, in their plasma and lung tissue. Sitaxentan blocks the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects. Sitaxentan is a competitive antagonist of endothelin-1 at the endothelin-A (ET-A) and endothelin-B (ET-B) receptors. Under normal conditions, endothelin-1 binding of ET-A or ET-B receptors causes pulmonary vasoconstriction. By blocking this interaction, Sitaxentan decreases pulmonary vascular resistance. Sitaxentan has a higher affinity for ET-A than ET-B. Hepatic (CYP2C9- and CYP3A4-mediated) 70-100% 10 hours 99% + Renal (50 to 60%) Fecal (40 to 50%) This compound belongs to the benzodioxoles. These are organic compounds containing a benzene ring fused to either isomers of dioxole. Benzodioxoles Organic Compounds Heterocyclic Compounds Benzodioxoles Toluenes Alkyl Aryl Ethers Aryl Chlorides Sulfonamides Sulfonyls Thiophenes Isoxazoles Ketones Enolates Polyamines Acetals Organochlorides toluene alkyl aryl ether aryl halide aryl chloride benzene isoxazole thiophene azole sulfonic acid derivative sulfonamide sulfonyl ketone enolate ether acetal polyamine carbonyl group organohalogen organochloride amine organonitrogen compound Sitaxentan Sitaxsentan Thelin Thelin CARDIOVASCULAR SYSTEM ANTIHYPERTENSIVES OTHER ANTIHYPERTENSIVES Other antihypertensives 2281090 Canada 2005-06-07 2018-04-02 2161346 Canada 2004-11-23 2014-05-20 Take without regard to meals DB00395 Carisoprodol Strong CYP2C19 inhibitors such as sitaxentan may decrease the metabolism of CYP2C19 substrates such as carisoprodol. Consider an alternative for one of the interacting drugs in order to avoid toxicity of the substrate. Some combinations are specifically contraindicated by manufacturers. Suggested dosage adjustments are also offered by some manufacturers. Please review applicable package inserts. Monitor for increased effects of the CYP substrate if a CYP inhibitor is initiated/dose increased, and decreased effects if a CYP inhibitor is discontinued/dose decreased. DB00675 Tamoxifen Sitaxsentan may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Sitaxsentan is initiated, discontinued or dose changed. DB00706 Tamsulosin Sitaxsentan, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Sitaxsentan is initiated, discontinued, or dose changed. DB08895 Tofacitinib Sitaxentan (moderate CYP3A4 inhibitors, strong CYP2C19 inhbitors), when used in combination with tofacitinib, may increase tofaciitinib serum concentration toxicity and adverse effects. It is recommended to adjust therapy by reducing the adult dose of tofacitinib from 5mg twice a day to 5 mg daily. DB01124 Tolbutamide Sitaxsentan, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Sitaxsentan is initiated, discontinued or dose changed. DB01036 Tolterodine Sitaxsentan may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity. DB00214 Torasemide Sitaxsentan, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Sitaxsentan is initiated, discontinued or dose changed. DB00193 Tramadol Sitaxsentan may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. DB00656 Trazodone The CYP3A4 inhibitor, Sitaxsenten, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Norfloxacin is initiated, discontinued or dose changed. DB00440 Trimethoprim The strong CYP2C9 inhibitor, Sitaxsentan, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Sitaxsentan is initiated, discontinued or dose changed. DB00726 Trimipramine The strong CYP2C19 inhibitor, Sitaxsentan, may decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Sitaxsentan is initiated, discontinued or dose changed. DB00582 Voriconazole Sitaxsentan, a strong CYP2C9 inhibitor, may increase the serum concentration of voriconazole by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of voriconazole if sitaxsentan is initiated, discontinued or dose changed. DB00682 Warfarin Sitaxentan, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Warfarin doses should be decreased by 80% upon initiated of concomitant therapy. Monitor for changes in the therapeutic and adverse effects of warfarin if sitaxentan is initiated, discontinued or dose changed. DB00549 Zafirlukast Sitaxentan, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if sitaxentan is initiated, discontinued or dose changed. logP 3.35 ALOGPS logS -4.4 ALOGPS Water Solubility 1.81e-02 g/l ALOGPS logP 3.09 ChemAxon IUPAC Name N-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-[2-(6-methyl-2H-1,3-benzodioxol-5-yl)acetyl]thiophene-3-sulfonamide ChemAxon Traditional IUPAC Name sitaxentan ChemAxon Molecular Weight 454.905 ChemAxon Monoisotopic Weight 454.006005309 ChemAxon SMILES CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC2=CC3=C(OCO3)C=C2C)=C1Cl ChemAxon Molecular Formula C18H15ClN2O6S2 ChemAxon InChI InChI=1S/C18H15ClN2O6S2/c1-9-5-13-14(26-8-25-13)7-11(9)6-12(22)17-15(3-4-28-17)29(23,24)21-18-16(19)10(2)20-27-18/h3-5,7,21H,6,8H2,1-2H3 ChemAxon InChIKey InChIKey=PHWXUGHIIBDVKD-UHFFFAOYSA-N ChemAxon Polar Surface Area (PSA) 107.73 ChemAxon Refractivity 105.8 ChemAxon Polarizability 43.12 ChemAxon Rotatable Bond Count 5 ChemAxon H Bond Acceptor Count 6 ChemAxon H Bond Donor Count 1 ChemAxon pKa (strongest acidic) 6.89 ChemAxon pKa (strongest basic) 0.75 ChemAxon Physiological Charge -1 ChemAxon Number of Rings 4 ChemAxon Bioavailability 1 ChemAxon Rule of Five true ChemAxon Ghose Filter true ChemAxon ChEBI 123417 PubChem Compound 216235 PubChem Substance 99443241 KEGG Drug D07171 ChemSpider 187436 BindingDB 50058126 PharmGKB PA165958361 IUPHAR 3950 Guide to Pharmacology 3950 Wikipedia Sitaxentan BE0000521 Endothelin-1 receptor Human antagonist # Girgis RE, Frost AE, Hill NS, Horn EM, Langleben D, McLaughlin VV, Oudiz RJ, Robbins IM, Seibold JR, Shapiro S, Tapson VF, Barst RJ: Selective endothelin A receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease. Ann Rheum Dis. 2007 Nov;66(11):1467-72. Epub 2007 May 1. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/17472992 # Albertini M, Lafortuna CL, Ciminaghi B, Mazzola S, Clement MG: Endothelin involvement in respiratory centre activity. Prostaglandins Leukot Essent Fatty Acids. 2001 Sep;65(3):157-63. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11728166 # Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11752352 # Kiowski W, Sutsch G, Oechslin E, Bertel O: Hemodynamic effects of bosentan in patients with chronic heart failure. Heart Fail Rev. 2001 Dec;6(4):325-34. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11447307 # Kramp R, Fourmanoir P, Caron N: Endothelin resets renal blood flow autoregulatory efficiency during acute blockade of NO in the rat. Am J Physiol Renal Physiol. 2001 Dec;281(6):F1132-40. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11704565 # Martin C, Held HD, Uhlig S: Differential effects of the mixed ET(A)/ET(B)-receptor antagonist bosentan on endothelin-induced bronchoconstriction, vasoconstriction and prostacyclin release. Naunyn Schmiedebergs Arch Pharmacol. 2000 Aug;362(2):128-36. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/10961375 # Sihvola RK, Pulkkinen VP, Koskinen PK, Lemstrom KB: Crosstalk of endothelin-1 and platelet-derived growth factor in cardiac allograft arteriosclerosis. J Am Coll Cardiol. 2002 Feb 20;39(4):710-7. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11849873 yes Endothelin-1 receptor Involved in endothelin receptor activity Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. The rank order of binding affinities for ET-A is:ET1 > ET2 >> ET3 EDNRA 4q31.23 Membrane; multi-pass membrane protein 81-102 113-132 160-181 206-229 257-278 307-328 348-372 8.41 48723.0 Human HUGO Gene Nomenclature Committee (HGNC) HGNC:3179 GenAtlas EDNRA GeneCards EDNRA GenBank Gene Database S63938 GenBank Protein Database 238636 IUPHAR 219 Guide to Pharmacology 21 UniProtKB P25101 UniProt Accession EDNRA_HUMAN Endothelin A receptor Endothelin-1 receptor precursor ET-A ETA-R hET- AR >Endothelin-1 receptor precursor METLCLRASFWLALVGCVISDNPERYSTNLSNHVDDFTTFRGTELSFLVTTHQPTNLVLP SNGSMHNYCPQQTKITSAFKYINTVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIA SLALGDLIYVVIDLPINVFKLLAGRWPFDHNDFGVFLCKLFPFLQKSSVGITVLNLCALS VDRYRAVASWSRVQGIGIPLVTAIEIVSIWILSFILAIPEAIGFVMVPFEYRGEQHKTCM LNATSKFMEFYQDVKDWWLFGFYFCMPLVCTAIFYTLMTCEMLNRRNGSLRIALSEHLKQ RREVAKTVFCLVVIFALCWFPLHLSRILKKTVYNEMDKNRCELLSFLLLMDYIGINLATM NSCINPIALYFVSKKFKNCFQSCLCCCCYQSKSLMTSVPMNGTSIQWKNHDQNNHNTDRS SHKDSMN >1284 bp ATGGAAACCCTTTGCCTCAGGGCATCCTTTTGGCTGGCACTGGTTGGATGTGTAATCAGT GATAATCCTGAGAGATACAGCACAAATCTAAGCAATCATGTGGATGATTTCACCACTTTT CGTGGCACAGAGCTCAGCTTCCTGGTTACCACTCATCAACCCACTAATTTGGTCCTACCC AGCAATGGCTCAATGCACAACTATTGCCCACAGCAGACTAAAATTACTTCAGCTTTCAAA TACATTAACACTGTGATATCTTGTACTATTTTCATCGTGGGAATGGTGGGGAATGCAACT CTGCTCAGGATCATTTACCAGAACAAATGTATGAGGAATGGCCCCAACGCGCTGATAGCC AGTCTTGCCCTTGGAGACCTTATCTATGTGGTCATTGATCTCCCTATCAATGTATTTAAG CTGCTGGCTGGGCGCTGGCCTTTTGATCACAATGACTTTGGCGTATTTCTTTGCAAGCTG TTCCCCTTTTTGCAGAAGTCCTCGGTGGGGATCACCGTCCTCAACCTCTGCGCTCTTAGT GTTGACAGGTACAGAGCAGTTGCCTCCTGGAGTCGTGTTCAGGGAATTGGGATTCCTTTG GTAACTGCCATTGAAATTGTCTCCATCTGGATCCTGTCCTTTATCCTGGCCATTCCTGAA GCGATTGGCTTCGTCATGGTACCCTTTGAATATAGGGGTGAACAGCATAAAACCTGTATG CTCAATGCCACATCAAAATTCATGGAGTTCTACCAAGATGTAAAGGACTGGTGGCTCTTC GGGTTCTATTTCTGTATGCCCTTGGTGTGCACTGCGATCTTCTACACCCTCATGACTTGT GAGATGTTGAACAGAAGGAATGGCAGCTTGAGAATTGCCCTCAGTGAACATCTTAAGCAG CGTCGAGAAGTGGCAAAAACAGTTTTCTGCTTGGTTGTAATTTTTGCTCTTTGCTGGTTC CCTCTTCATTTAAGCCGTATATTGAAGAAAACTGTGTATAACGAGATGGACAAGAACCGA TGTGAATTACTTAGTTTCTTACTGCTCATGGATTACATCGGTATTAACTTGGCAACCATG AATTCATGTATAAACCCCATAGCTCTGTATTTTGTGAGCAAGAAATTTAAAAATTGTTTC CAGTCATGCCTCTGCTGCTGCTGTTACCAGTCCAAAAGTCTGATGACCTCGGTCCCCATG AACGGAACAAGCATCCAGTGGAAGAACCACGATCAAAACAACCACAACACAGACCGGAGC AGCCATAAGGACAGCATGAACTGA PF00001 7tm_1 component integral to membrane component membrane component cell component intrinsic to membrane function peptide receptor activity, G-protein coupled function signal transducer activity function endothelin receptor activity function receptor activity function transmembrane receptor activity function G-protein coupled receptor activity function rhodopsin-like receptor activity process cell surface receptor linked signal transduction process G-protein coupled receptor protein signaling pathway process cellular process process cell communication process signal transduction BE0000043 Endothelin B receptor Human antagonist # Girgis RE, Frost AE, Hill NS, Horn EM, Langleben D, McLaughlin VV, Oudiz RJ, Robbins IM, Seibold JR, Shapiro S, Tapson VF, Barst RJ: Selective endothelin A receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease. Ann Rheum Dis. 2007 Nov;66(11):1467-72. Epub 2007 May 1. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/17472992 # Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11752352 # Gardiner SM, Kemp PA, March JE, Bennett T: Effects of bosentan (Ro 47-0203), an ETA-, ETB-receptor antagonist, on regional haemodynamic responses to endothelins in conscious rats. Br J Pharmacol. 1994 Jul;112(3):823-30. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/7921608 # Gupta SK, Saxena A, Singh U, Arya DS: Bosentan, the mixed ETA-ETB endothelin receptor antagonist, attenuated oxidative stress after experimental myocardial ischemia and reperfusion. Mol Cell Biochem. 2005 Jul;275(1-2):67-74. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/16335785 # Marano G, Palazzesi S, Bernucci P, Grigioni M, Formigari R, Ballerini L: ET(A)/ET(B) receptor antagonist bosentan inhibits neointimal development in collared carotid arteries of rabbits. Life Sci. 1998;63(18):PL259-66. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/9806221 # Richard V, Kaeffer N, Hogie M, Tron C, Blanc T, Thuillez C: Role of endogenous endothelin in myocardial and coronary endothelial injury after ischaemia and reperfusion in rats: studies with bosentan, a mixed ETA-ETB antagonist. Br J Pharmacol. 1994 Nov;113(3):869-76. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/7858879 # Said SA, Ammar el SM, Suddek GM: Effect of bosentan (ETA/ETB receptor antagonist) on metabolic changes during stress and diabetes. Pharmacol Res. 2005 Feb;51(2):107-15. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/15629255 unknown Endothelin B receptor Involved in endothelin receptor activity Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system EDNRB 13q22 Membrane; multi-pass membrane protein 102-126 138-163 176-197 219-243 272-296 325-350 363-389 9.05 49644.0 Human HUGO Gene Nomenclature Committee (HGNC) HGNC:3180 GenAtlas EDNRB GeneCards EDNRB GenBank Gene Database M74921 GenBank Protein Database 182276 IUPHAR 220 Guide to Pharmacology 21 UniProtKB P24530 UniProt Accession EDNRB_HUMAN Endothelin B receptor precursor Endothelin receptor Non- selective type ET-B >Endothelin B receptor precursor MQPPPSLCGRALVALVLACGLSRIWGEERGFPPDRATPLLQTAEIMTPPTKTLWPKGSNA SLARSLAPAEVPKGDRTAGSPPRTISPPPCQGPIEIKETFKYINTVVSCLVFVLGIIGNS TLLRIIYKNKCMRNGPNILIASLALGDLLHIVIDIPINVYKLLAEDWPFGAEMCKLVPFI QKASVGITVLSLCALSIDRYRAVASWSRIKGIGVPKWTAVEIVLIWVVSVVLAVPEAIGF DIITMDYKGSYLRICLLHPVQKTAFMQFYKTAKDWWLFSFYFCLPLAITAFFYTLMTCEM LRKKSGMQIALNDHLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTLYNQNDPNRCEL LSFLLVLDYIGINMASLNSCINPIALYLVSKRFKNCFKSCLCCWCQSFEEKQSLEEKQSC LKFKANDHGYDNFRSSNKYSSS >1329 bp ATGCAGCCGCCTCCAAGTCTGTGCGGACGCGCCCTGGTTGCGCTGGTTCTTGCCTGCGGC CTGTCGCGGATCTGGGGAGAGGAGAGAGGCTTCCCGCCTGACAGGGCCACTCCGCTTTTG CAAACCGCAGAGATAATGACGCCACCCACTAAGACCTTATGGCCCAAGGGTTCCAACGCC AGTCTGGCGCGGTCGTTGGCACCTGCGGAGGTGCCTAAAGGAGACAGGACGGCAGGATCT CCGCCACGCACCATCTCCCCTCCCCCGTGCCAAGGACCCATCGAGATCAAGGAGACTTTC AAATACATCAACACGGTTGTGTCCTGCCTTGTGTTCGTGCTGGGGATCATCGGGAACTCC ACACTTCTGAGAATTATCTACAAGAACAAGTGCATGCGAAACGGTCCCAATATCTTGATC GCCAGCTTGGCTCTGGGAGACCTGCTGCACATCGTCATTGACATCCCTATCAATGTCTAC AAGCTGCTGGCAGAGGACTGGCCATTTGGAGCTGAGATGTGTAAGCTGGTGCCTTTCATA CAGAAAGCCTCCGTGGGAATCACTGTGCTGAGTCTATGTGCTCTGAGTATTGACAGATAT CGAGCTGTTGCTTCTTGGAGTAGAATTAAAGGAATTGGGGTTCCAAAATGGACAGCAGTA GAAATTGTTTTGATTTGGGTGGTCTCTGTGGTTCTGGCTGTCCCTGAAGCCATAGGTTTT GATATAATTACGATGGACTACAAAGGAAGTTATCTGCGAATCTGCTTGCTTCATCCCGTT CAGAAGACAGCTTTCATGCAGTTTTACAAGACAGCAAAAGATTGGTGGCTGTTCAGTTTC TATTTCTGCTTGCCATTGGCCATCACTGCATTTTTTTATACACTAATGACCTGTGAAATG TTGAGAAAGAAAAGTGGCATGCAGATTGCTTTAAATGATCACCTAAAGCAGAGACGGGAA GTGGCCAAAACCGTCTTTTGCCTGGTCCTTGTCTTTGCCCTCTGCTGGCTTCCCCTTCAC CTCAGCAGGATTCTGAAGCTCACTCTTTATAATCAGAATGATCCCAATAGATGTGAACTT TTGAGCTTTCTGTTGGTATTGGACTATATTGGTATCAACATGGCTTCACTGAATTCCTGC ATTAACCCAATTGCTCTGTATTTGGTGAGCAAAAGATTCAAAAACTGCTTTAAGTCATGC TTATGCTGCTGGTGCCAGTCATTTGAAGAAAAACAGTCCTTGGAGGAAAAGCAGTCGTGC TTAAAGTTCAAAGCTAATGATCACGGATATGACAACTTCCGTTCCAGTAATAAATACAGC TCATCTTGA PF00001 7tm_1 component cell component intrinsic to membrane component integral to membrane component membrane function receptor activity function transmembrane receptor activity function G-protein coupled receptor activity function rhodopsin-like receptor activity function peptide receptor activity, G-protein coupled function signal transducer activity function endothelin receptor activity process cellular process process cell communication process signal transduction process cell surface receptor linked signal transduction process G-protein coupled receptor protein signaling pathway BE0002793 Cytochrome P450 2C9 Human substrate inhibitor # Pulido T, Sandoval J, Roquet I, Gutierrez R, Rueda T, Pena H, Santos E, Miranda MT, Lupi E: Interaction of acenocoumarol and sitaxentan in pulmonary arterial hypertension. Eur J Clin Invest. 2009 Jun;39 Suppl 2:14-8. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/19335742 # Opitz CF, Ewert R, Kirch W, Pittrow D: Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter? Eur Heart J. 2008 Aug;29(16):1936-48. Epub 2008 Jun 17. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/18562303 # Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarlin J: Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study. Chest. 2002 Jun;121(6):1860-8. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/12065350 unknown Cytochrome P450 2C9 Involved in monooxygenase activity 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 CYP2C9 10q24 Endoplasmic reticulum None 7.99 55629.0 Human HUGO Gene Nomenclature Committee (HGNC) HGNC:2623 GenAtlas CYP2C9 GenBank Gene Database AY341248 UniProtKB P11712 UniProt Accession CP2C9_HUMAN (R)-limonene 6-monooxygenase (S)- limonene 7-monooxygenase (S)-limonene 6-monooxygenase CYPIIC9 EC 1.14.13.48 EC 1.14.13.49 EC 1.14.13.80 P-450MP P450 MP-4/MP-8 P450 PB-1 S- mephenytoin 4-hydroxylase >Cytochrome P450 2C9 MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKV YGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKW KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS IIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFM KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTE TTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYID LLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK KSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP PFYQLCFIPV >1473 bp ATGGATTCTCTTGTGGTCCTTGTGCTCTGTCTCTCATGTTTGCTTCTCCTTTCACTCTGG AGACAGAGCTCTGGGAGAGGAAAACTCCCTCCTGGCCCCACTCCTCTCCCAGTGATTGGA AATATCCTACAGATAGGTATTAAGGACATCAGCAAATCCTTAACCAATCTCTCAAAGGTC TATGGCCCTGTGTTCACTCTGTATTTTGGCCTGAAACCCATAGTGGTGCTGCATGGATAT GAAGCAGTGAAGGAAGCCCTGATTGATCTTGGAGAGGAGTTTTCTGGAAGAGGCATTTTC CCACTGGCTGAAAGAGCTAACAGAGGATTTGGAATTGTTTTCAGCAATGGAAAGAAATGG AAGGAGATCCGGCGTTTCTCCCTCATGACGCTGCGGAATTTTGGGATGGGGAAGAGGAGC ATTGAGGACCGTGTTCAAGAGGAAGCCCGCTGCCTTGTGGAGGAGTTGAGAAAAACCAAG GCCTCACCCTGTGATCCCACTTTCATCCTGGGCTGTGCTCCCTGCAATGTGATCTGCTCC ATTATTTTCCATAAACGTTTTGATTATAAAGATCAGCAATTTCTTAACTTAATGGAAAAG TTGAATGAAAACATCAAGATTTTGAGCAGCCCCTGGATCCAGATCTGCAATAATTTTTCT CCTATCATTGATTACTTCCCGGGAACTCACAACAAATTACTTAAAAACGTTGCTTTTATG AAAAGTTATATTTTGGAAAAAGTAAAAGAACACCAAGAATCAATGGACATGAACAACCCT CAGGACTTTATTGATTGCTTCCTGATGAAAATGGAGAAGGAAAAGCACAACCAACCATCT GAATTTACTATTGAAAGCTTGGAAAACACTGCAGTTGACTTGTTTGGAGCTGGGACAGAG ACGACAAGCACAACCCTGAGATATGCTCTCCTTCTCCTGCTGAAGCACCCAGAGGTCACA GCTAAAGTCCAGGAAGAGATTGAACGTGTGATTGGCAGAAACCGGAGCCCCTGCATGCAA GACAGGAGCCACATGCCCTACACAGATGCTGTGGTGCACGAGGTCCAGAGATACATTGAC CTTCTCCCCACCAGCCTGCCCCATGCAGTGACCTGTGACATTAAATTCAGAAACTATCTC ATTCCCAAGGGCACAACCATATTAATTTCCCTGACTTCTGTGCTACATGACAACAAAGAA TTTCCCAACCCAGAGATGTTTGACCCTCATCACTTTCTGGATGAAGGTGGCAATTTTAAG AAAAGTAAATACTTCATGCCTTTCTCAGCAGGAAAACGGATTTGTGTGGGAGAAGCCCTG GCCGGCATGGAGCTGTTTTTATTCCTGACCTCCATTTTACAGAACTTTAACCTGAAATCT CTGGTTGACCCAAAGAACCTTGACACCACTCCAGTTGTCAATGGATTTGCCTCTGTGCCG CCCTTCTACCAGCTGTGCTTCATTCCTGTCTGA PF00067 p450 function cation binding function transition metal ion binding function iron ion binding function binding function tetrapyrrole binding function catalytic activity function heme binding function monooxygenase activity function oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen function oxidoreductase activity function ion binding process generation of precursor metabolites and energy process electron transport process physiological process process metabolism process cellular metabolism unknown unknown BE0002638 Cytochrome P450 3A4 Human inhibitor # Stavros F, Kramer WG, Wilkins MR: The effects of sitaxentan on sildenafil pharmacokinetics and pharmacodynamics in healthy subjects. Br J Clin Pharmacol. 2010 Jan;69(1):23-6. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/20078609 # Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarlin J: Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study. Chest. 2002 Jun;121(6):1860-8. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/12065350 unknown Cytochrome P450 3A4 Involved in monooxygenase activity 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 CYP3A4 7q21.1 Endoplasmic reticulum 2-22 8.25 57344.0 Human HUGO Gene Nomenclature Committee (HGNC) HGNC:2637 GenAtlas CYP3A4 GenBank Gene Database M18907 UniProtKB P08684 UniProt Accession CP3A4_HUMAN CYPIIIA4 EC 1.14.13.67 EC 1.14.13.97 NF-25 Nifedipine oxidase P450-PCN1 Quinine 3-monooxygenase Taurochenodeoxycholate 6-alpha- hydroxylase >Cytochrome P450 3A4 MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMF DMECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISI AEDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYS MDVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICV FPREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSI IFIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVV NETLRLFPIAMRLERVCKKDVEINGMFIPKGVVVMIPSYALHRDPKYWTEPEKFLPERFS KKNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLG GLLQPEKPVVLKVESRDGTVSGA >1512 bp ATGGCTCTCATCCCAGACTTGGCCATGGAAACCTGGCTTCTCCTGGCTGTCAGCCTGGTG CTCCTCTATCTATATGGAACCCATTCACATGGACTTTTTAAGAAGCTTGGAATTCCAGGG CCCACACCTCTGCCTTTTTTGGGAAATATTTTGTCCTACCATAAGGGCTTTTGTATGTTT GACATGGAATGTCATAAAAAGTATGGAAAAGTGTGGGGCTTTTATGATGGTCAACAGCCT GTGCTGGCTATCACAGATCCTGACATGATCAAAACAGTGCTAGTGAAAGAATGTTATTCT GTCTTCACAAACCGGAGGCCTTTTGGTCCAGTGGGATTTATGAAAAGTGCCATCTCTATA GCTGAGGATGAAGAATGGAAGAGATTACGATCATTGCTGTCTCCAACCTTCACCAGTGGA AAACTCAAGGAGATGGTCCCTATCATTGCCCAGTATGGAGATGTGTTGGTGAGAAATCTG AGGCGGGAAGCAGAGACAGGCAAGCCTGTCACCTTGAAAGACGTCTTTGGGGCCTACAGC ATGGATGTGATCACTAGCACATCATTTGGAGTGAACATCGACTCTCTCAACAATCCACAA GACCCCTTTGTGGAAAACACCAAGAAGCTTTTAAGATTTGATTTTTTGGATCCATTCTTT CTCTCAATAACAGTCTTTCCATTCCTCATCCCAATTCTTGAAGTATTAAATATCTGTGTG TTTCCAAGAGAAGTTACAAATTTTTTAAGAAAATCTGTAAAAAGGATGAAAGAAAGTCGC CTCGAAGATACACAAAAGCACCGAGTGGATTTCCTTCAGCTGATGATTGACTCTCAGAAT TCAAAAGAAACTGAGTCCCACAAAGCTCTGTCCGATCTGGAGCTCGTGGCCCAATCAATT ATCTTTATTTTTGCTGGCTATGAAACCACGAGCAGTGTTCTCTCCTTCATTATGTATGAA CTGGCCACTCACCCTGATGTCCAGCAGAAACTGCAGGAGGAAATTGATGCAGTTTTACCC AATAAGGCACCACCCACCTATGATACTGTGCTACAGATGGAGTATCTTGACATGGTGGTG AATGAAACGCTCAGATTATTCCCAATTGCTATGAGACTTGAGAGGGTCTGCAAAAAAGAT GTTGAGATCAATGGGATGTTCATTCCCAAAGGGGTGGTGGTGATGATTCCAAGCTATGCT CTTCACCGTGACCCAAAGTACTGGACAGAGCCTGAGAAGTTCCTCCCTGAAAGATTCAGC AAGAAGAACAAGGACAACATAGATCCTTACATATACACACCCTTTGGAAGTGGACCCAGA AACTGCATTGGCATGAGGTTTGCTCTCATGAACATGAAACTTGCTCTAATCAGAGTCCTT CAGAACTTCTCCTTCAAACCTTGTAAAGAAACACAGATCCCCCTGAAATTAAGCTTAGGA GGACTTCTTCAACCAGAAAAACCCGTTGTTCTAAAGGTTGAGTCAAGGGATGGCACCGTA AGTGGAGCCTGA PF00067 p450 function oxidoreductase activity function ion binding function cation binding function transition metal ion binding function iron ion binding function binding function tetrapyrrole binding function catalytic activity function heme binding function monooxygenase activity function oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen process generation of precursor metabolites and energy process electron transport process physiological process process metabolism process cellular metabolism unknown unknown BE0003536 Cytochrome P450 2C19 Human inhibitor # Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarlin J: Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study. Chest. 2002 Jun;121(6):1860-8. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/12065350 unknown Cytochrome P450 2C19 Secondary metabolites biosynthesis, transport and catabolism 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 CYP2C19 10q24.1-q24.3 Endoplasmic reticulum membrane None 7.42 55930.5 Human HUGO Gene Nomenclature Committee (HGNC) GNC:2621 GeneCards CYP2C19 GenBank Gene Database M61854 GenBank Protein Database 181344 UniProtKB P33261 UniProt Accession CP2CJ_HUMAN (R)-limonene 6-monooxygenase (S)-limonene 6-monooxygenase (S)-limonene 7-monooxygenase CYPIIC17 CYPIIC19 Mephenytoin 4-hydroxylase P450-11A P450-254C >Cytochrome P450 2C19 MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDVSKSLTNLSKI YGPVFTLYFGLERMVVLHGYEVVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKRW KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS IIFQKRFDYKDQQFLNLMEKLNENIRIVSTPWIQICNNFPTIIDYFPGTHNKLLKNLAFM ESDILEKVKEHQESMDINNPRDFIDCFLIKMEKEKQNQQSEFTIENLVITAADLLGAGTE TTSTTLRYALLLLLKHPEVTAKVQEEIERVVGRNRSPCMQDRGHMPYTDAVVHEVQRYID LIPTSLPHAVTCDVKFRNYLIPKGTTILTSLTSVLHDNKEFPNPEMFDPRHFLDEGGNFK KSNYFMPFSAGKRICVGEGLARMELFLFLTFILQNFNLKSLIDPKDLDTTPVVNGFASVP PFYQLCFIPV >1473 bp ATGGATCCTTTTGTGGTCCTTGTGCTCTGTCTCTCATGTTTGCTTCTCCTTTCAATCTGG AGACAGAGCTCTGGGAGAGGAAAACTCCCTCCTGGCCCCACTCCTCTCCCAGTGATTGGA AATATCCTACAGATAGATATTAAGGATGTCAGCAAATCCTTAACCAATCTCTCAAAAATC TATGGCCCTGTGTTCACTCTGTATTTTGGCCTGGAACGCATGGTGGTGCTGCATGGATAT GAAGTGGTGAAGGAAGCCCTGATTGATCTTGGAGAGGAGTTTTCTGGAAGAGGCCATTTC CCACTGGCTGAAAGAGCTAACAGAGGATTTGGAATCGTTTTCAGCAATGGAAAGAGATGG AAGGAGATCCGGCGTTTCTCCCTCATGACGCTGCGGAATTTTGGGATGGGGAAGAGGAGC ATTGAGGACCGTGTTCAAGAGGAAGCCCGCTGCCTTGTGGAGGAGTTGAGAAAAACCAAG GCTTCACCCTGTGATCCCACTTTCATCCTGGGCTGTGCTCCCTGCAATGTGATCTGCTCC ATTATTTTCCAGAAACGTTTCGATTATAAAGATCAGCAATTTCTTAACTTGATGGAAAAA TTGAATGAAAACATCAGGATTGTAAGCACCCCCTGGATCCAGATATGCAATAATTTTCCC ACTATCATTGATTATTTCCCGGGAACCCATAACAAATTACTTAAAAACCTTGCTTTTATG GAAAGTGATATTTTGGAGAAAGTAAAAGAACACCAAGAATCGATGGACATCAACAACCCT CGGGACTTTATTGATTGCTTCCTGATCAAAATGGAGAAGGAAAAGCAAAACCAACAGTCT GAATTCACTATTGAAAACTTGGTAATCACTGCAGCTGACTTACTTGGAGCTGGGACAGAG ACAACAAGCACAACCCTGAGATATGCTCTCCTTCTCCTGCTGAAGCACCCAGAGGTCACA GCTAAAGTCCAGGAAGAGATTGAACGTGTCATTGGCAGAAACCGGAGCCCCTGCATGCAG GACAGGGGCCACATGCCCTACACAGATGCTGTGGTGCACGAGGTCCAGAGATACATCGAC CTCATCCCCACCAGCCTGCCCCATGCAGTGACCTGTGACGTTAAATTCAGAAACTACCTC ATTCCCAAGGGCACAACCATATTAACTTCCCTCACTTCTGTGCTACATGACAACAAAGAA TTTCCCAACCCAGAGATGTTTGACCCTCGTCACTTTCTGGATGAAGGTGGAAATTTTAAG AAAAGTAACTACTTCATGCCTTTCTCAGCAGGAAAACGGATTTGTGTGGGAGAGGGCCTG GCCCGCATGGAGCTGTTTTTATTCCTGACCTTCATTTTACAGAACTTTAACCTGAAATCT CTGATTGACCCAAAGGACCTTGACACAACTCCTGTTGTCAATGGATTTGCTTCTGTCCCG CCCTTCTATCAGCTGTGCTTCATTCCTGTCTGA PF00067 p450 function catalytic activity function heme binding function monooxygenase activity function oxidoreductase activity function ion binding function cation binding function transition metal ion binding function iron ion binding function binding function tetrapyrrole binding process metabolism process cellular metabolism process generation of precursor metabolites and energy process electron transport process physiological process unknown unknown "
drugbank:interactsWith	drug:Tramadol drug:Torasemide drug:Carisoprodol drug:Trimethoprim drug:Zafirlukast drug:Voriconazole drug:Trazodone drug:Tamoxifen drug:Warfarin drug:Tamsulosin drug:Trimipramine drug:Tolterodine drug:Tolbutamide drug:Tofacitinib
owl:sameAs	drug:Tramadol drug:Torasemide drug:Carisoprodol drug:Trimethoprim drug:Zafirlukast drug:Voriconazole drug:Trazodone drug:Tamoxifen drug:Warfarin drug:Tamsulosin drug:Trimipramine drug:Tolterodine drug:Tolbutamide drug:Tofacitinib

"Sitaxentan"

" 210421-64-0 approved investigational Investigated for use/treatment in pulmonary hypertension, connective tissue diseases, hypertension, and congestive heart failure. Sitaxentan belongs to a class of drugs known as endothelin receptor antagonists (ERAs). Patients with PAH have elevated levels of endothelin, a potent blood vessel constrictor, in their plasma and lung tissue. Sitaxentan blocks the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects. Sitaxentan is a competitive antagonist of endothelin-1 at the endothelin-A (ET-A) and endothelin-B (ET-B) receptors. Under normal conditions, endothelin-1 binding of ET-A or ET-B receptors causes pulmonary vasoconstriction. By blocking this interaction, Sitaxentan decreases pulmonary vascular resistance. Sitaxentan has a higher affinity for ET-A than ET-B. Hepatic (CYP2C9- and CYP3A4-mediated) 70-100% 10 hours 99% + Renal (50 to 60%) Fecal (40 to 50%) This compound belongs to the benzodioxoles. These are organic compounds containing a benzene ring fused to either isomers of dioxole. Benzodioxoles Organic Compounds Heterocyclic Compounds Benzodioxoles Toluenes Alkyl Aryl Ethers Aryl Chlorides Sulfonamides Sulfonyls Thiophenes Isoxazoles Ketones Enolates Polyamines Acetals Organochlorides toluene alkyl aryl ether aryl halide aryl chloride benzene isoxazole thiophene azole sulfonic acid derivative sulfonamide sulfonyl ketone enolate ether acetal polyamine carbonyl group organohalogen organochloride amine organonitrogen compound Sitaxentan Sitaxsentan Thelin Thelin CARDIOVASCULAR SYSTEM ANTIHYPERTENSIVES OTHER ANTIHYPERTENSIVES Other antihypertensives 2281090 Canada 2005-06-07 2018-04-02 2161346 Canada 2004-11-23 2014-05-20 Take without regard to meals DB00395 Carisoprodol Strong CYP2C19 inhibitors such as sitaxentan may decrease the metabolism of CYP2C19 substrates such as carisoprodol. Consider an alternative for one of the interacting drugs in order to avoid toxicity of the substrate. Some combinations are specifically contraindicated by manufacturers. Suggested dosage adjustments are also offered by some manufacturers. Please review applicable package inserts. Monitor for increased effects of the CYP substrate if a CYP inhibitor is initiated/dose increased, and decreased effects if a CYP inhibitor is discontinued/dose decreased. DB00675 Tamoxifen Sitaxsentan may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Sitaxsentan is initiated, discontinued or dose changed. DB00706 Tamsulosin Sitaxsentan, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Sitaxsentan is initiated, discontinued, or dose changed. DB08895 Tofacitinib Sitaxentan (moderate CYP3A4 inhibitors, strong CYP2C19 inhbitors), when used in combination with tofacitinib, may increase tofaciitinib serum concentration toxicity and adverse effects. It is recommended to adjust therapy by reducing the adult dose of tofacitinib from 5mg twice a day to 5 mg daily. DB01124 Tolbutamide Sitaxsentan, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Sitaxsentan is initiated, discontinued or dose changed. DB01036 Tolterodine Sitaxsentan may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity. DB00214 Torasemide Sitaxsentan, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Sitaxsentan is initiated, discontinued or dose changed. DB00193 Tramadol Sitaxsentan may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. DB00656 Trazodone The CYP3A4 inhibitor, Sitaxsenten, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Norfloxacin is initiated, discontinued or dose changed. DB00440 Trimethoprim The strong CYP2C9 inhibitor, Sitaxsentan, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Sitaxsentan is initiated, discontinued or dose changed. DB00726 Trimipramine The strong CYP2C19 inhibitor, Sitaxsentan, may decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Sitaxsentan is initiated, discontinued or dose changed. DB00582 Voriconazole Sitaxsentan, a strong CYP2C9 inhibitor, may increase the serum concentration of voriconazole by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of voriconazole if sitaxsentan is initiated, discontinued or dose changed. DB00682 Warfarin Sitaxentan, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Warfarin doses should be decreased by 80% upon initiated of concomitant therapy. Monitor for changes in the therapeutic and adverse effects of warfarin if sitaxentan is initiated, discontinued or dose changed. DB00549 Zafirlukast Sitaxentan, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if sitaxentan is initiated, discontinued or dose changed. logP 3.35 ALOGPS logS -4.4 ALOGPS Water Solubility 1.81e-02 g/l ALOGPS logP 3.09 ChemAxon IUPAC Name N-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-[2-(6-methyl-2H-1,3-benzodioxol-5-yl)acetyl]thiophene-3-sulfonamide ChemAxon Traditional IUPAC Name sitaxentan ChemAxon Molecular Weight 454.905 ChemAxon Monoisotopic Weight 454.006005309 ChemAxon SMILES CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC2=CC3=C(OCO3)C=C2C)=C1Cl ChemAxon Molecular Formula C18H15ClN2O6S2 ChemAxon InChI InChI=1S/C18H15ClN2O6S2/c1-9-5-13-14(26-8-25-13)7-11(9)6-12(22)17-15(3-4-28-17)29(23,24)21-18-16(19)10(2)20-27-18/h3-5,7,21H,6,8H2,1-2H3 ChemAxon InChIKey InChIKey=PHWXUGHIIBDVKD-UHFFFAOYSA-N ChemAxon Polar Surface Area (PSA) 107.73 ChemAxon Refractivity 105.8 ChemAxon Polarizability 43.12 ChemAxon Rotatable Bond Count 5 ChemAxon H Bond Acceptor Count 6 ChemAxon H Bond Donor Count 1 ChemAxon pKa (strongest acidic) 6.89 ChemAxon pKa (strongest basic) 0.75 ChemAxon Physiological Charge -1 ChemAxon Number of Rings 4 ChemAxon Bioavailability 1 ChemAxon Rule of Five true ChemAxon Ghose Filter true ChemAxon ChEBI 123417 PubChem Compound 216235 PubChem Substance 99443241 KEGG Drug D07171 ChemSpider 187436 BindingDB 50058126 PharmGKB PA165958361 IUPHAR 3950 Guide to Pharmacology 3950 Wikipedia Sitaxentan BE0000521 Endothelin-1 receptor Human antagonist # Girgis RE, Frost AE, Hill NS, Horn EM, Langleben D, McLaughlin VV, Oudiz RJ, Robbins IM, Seibold JR, Shapiro S, Tapson VF, Barst RJ: Selective endothelin A receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease. Ann Rheum Dis. 2007 Nov;66(11):1467-72. Epub 2007 May 1. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/17472992 # Albertini M, Lafortuna CL, Ciminaghi B, Mazzola S, Clement MG: Endothelin involvement in respiratory centre activity. Prostaglandins Leukot Essent Fatty Acids. 2001 Sep;65(3):157-63. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11728166 # Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11752352 # Kiowski W, Sutsch G, Oechslin E, Bertel O: Hemodynamic effects of bosentan in patients with chronic heart failure. Heart Fail Rev. 2001 Dec;6(4):325-34. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11447307 # Kramp R, Fourmanoir P, Caron N: Endothelin resets renal blood flow autoregulatory efficiency during acute blockade of NO in the rat. Am J Physiol Renal Physiol. 2001 Dec;281(6):F1132-40. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11704565 # Martin C, Held HD, Uhlig S: Differential effects of the mixed ET(A)/ET(B)-receptor antagonist bosentan on endothelin-induced bronchoconstriction, vasoconstriction and prostacyclin release. Naunyn Schmiedebergs Arch Pharmacol. 2000 Aug;362(2):128-36. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/10961375 # Sihvola RK, Pulkkinen VP, Koskinen PK, Lemstrom KB: Crosstalk of endothelin-1 and platelet-derived growth factor in cardiac allograft arteriosclerosis. J Am Coll Cardiol. 2002 Feb 20;39(4):710-7. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11849873 yes Endothelin-1 receptor Involved in endothelin receptor activity Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. The rank order of binding affinities for ET-A is:ET1 > ET2 >> ET3 EDNRA 4q31.23 Membrane; multi-pass membrane protein 81-102 113-132 160-181 206-229 257-278 307-328 348-372 8.41 48723.0 Human HUGO Gene Nomenclature Committee (HGNC) HGNC:3179 GenAtlas EDNRA GeneCards EDNRA GenBank Gene Database S63938 GenBank Protein Database 238636 IUPHAR 219 Guide to Pharmacology 21 UniProtKB P25101 UniProt Accession EDNRA_HUMAN Endothelin A receptor Endothelin-1 receptor precursor ET-A ETA-R hET- AR >Endothelin-1 receptor precursor METLCLRASFWLALVGCVISDNPERYSTNLSNHVDDFTTFRGTELSFLVTTHQPTNLVLP SNGSMHNYCPQQTKITSAFKYINTVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIA SLALGDLIYVVIDLPINVFKLLAGRWPFDHNDFGVFLCKLFPFLQKSSVGITVLNLCALS VDRYRAVASWSRVQGIGIPLVTAIEIVSIWILSFILAIPEAIGFVMVPFEYRGEQHKTCM LNATSKFMEFYQDVKDWWLFGFYFCMPLVCTAIFYTLMTCEMLNRRNGSLRIALSEHLKQ RREVAKTVFCLVVIFALCWFPLHLSRILKKTVYNEMDKNRCELLSFLLLMDYIGINLATM NSCINPIALYFVSKKFKNCFQSCLCCCCYQSKSLMTSVPMNGTSIQWKNHDQNNHNTDRS SHKDSMN >1284 bp ATGGAAACCCTTTGCCTCAGGGCATCCTTTTGGCTGGCACTGGTTGGATGTGTAATCAGT GATAATCCTGAGAGATACAGCACAAATCTAAGCAATCATGTGGATGATTTCACCACTTTT CGTGGCACAGAGCTCAGCTTCCTGGTTACCACTCATCAACCCACTAATTTGGTCCTACCC AGCAATGGCTCAATGCACAACTATTGCCCACAGCAGACTAAAATTACTTCAGCTTTCAAA TACATTAACACTGTGATATCTTGTACTATTTTCATCGTGGGAATGGTGGGGAATGCAACT CTGCTCAGGATCATTTACCAGAACAAATGTATGAGGAATGGCCCCAACGCGCTGATAGCC AGTCTTGCCCTTGGAGACCTTATCTATGTGGTCATTGATCTCCCTATCAATGTATTTAAG CTGCTGGCTGGGCGCTGGCCTTTTGATCACAATGACTTTGGCGTATTTCTTTGCAAGCTG TTCCCCTTTTTGCAGAAGTCCTCGGTGGGGATCACCGTCCTCAACCTCTGCGCTCTTAGT GTTGACAGGTACAGAGCAGTTGCCTCCTGGAGTCGTGTTCAGGGAATTGGGATTCCTTTG GTAACTGCCATTGAAATTGTCTCCATCTGGATCCTGTCCTTTATCCTGGCCATTCCTGAA GCGATTGGCTTCGTCATGGTACCCTTTGAATATAGGGGTGAACAGCATAAAACCTGTATG CTCAATGCCACATCAAAATTCATGGAGTTCTACCAAGATGTAAAGGACTGGTGGCTCTTC GGGTTCTATTTCTGTATGCCCTTGGTGTGCACTGCGATCTTCTACACCCTCATGACTTGT GAGATGTTGAACAGAAGGAATGGCAGCTTGAGAATTGCCCTCAGTGAACATCTTAAGCAG CGTCGAGAAGTGGCAAAAACAGTTTTCTGCTTGGTTGTAATTTTTGCTCTTTGCTGGTTC CCTCTTCATTTAAGCCGTATATTGAAGAAAACTGTGTATAACGAGATGGACAAGAACCGA TGTGAATTACTTAGTTTCTTACTGCTCATGGATTACATCGGTATTAACTTGGCAACCATG AATTCATGTATAAACCCCATAGCTCTGTATTTTGTGAGCAAGAAATTTAAAAATTGTTTC CAGTCATGCCTCTGCTGCTGCTGTTACCAGTCCAAAAGTCTGATGACCTCGGTCCCCATG AACGGAACAAGCATCCAGTGGAAGAACCACGATCAAAACAACCACAACACAGACCGGAGC AGCCATAAGGACAGCATGAACTGA PF00001 7tm_1 component integral to membrane component membrane component cell component intrinsic to membrane function peptide receptor activity, G-protein coupled function signal transducer activity function endothelin receptor activity function receptor activity function transmembrane receptor activity function G-protein coupled receptor activity function rhodopsin-like receptor activity process cell surface receptor linked signal transduction process G-protein coupled receptor protein signaling pathway process cellular process process cell communication process signal transduction BE0000043 Endothelin B receptor Human antagonist # Girgis RE, Frost AE, Hill NS, Horn EM, Langleben D, McLaughlin VV, Oudiz RJ, Robbins IM, Seibold JR, Shapiro S, Tapson VF, Barst RJ: Selective endothelin A receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease. Ann Rheum Dis. 2007 Nov;66(11):1467-72. Epub 2007 May 1. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/17472992 # Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11752352 # Gardiner SM, Kemp PA, March JE, Bennett T: Effects of bosentan (Ro 47-0203), an ETA-, ETB-receptor antagonist, on regional haemodynamic responses to endothelins in conscious rats. Br J Pharmacol. 1994 Jul;112(3):823-30. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/7921608 # Gupta SK, Saxena A, Singh U, Arya DS: Bosentan, the mixed ETA-ETB endothelin receptor antagonist, attenuated oxidative stress after experimental myocardial ischemia and reperfusion. Mol Cell Biochem. 2005 Jul;275(1-2):67-74. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/16335785 # Marano G, Palazzesi S, Bernucci P, Grigioni M, Formigari R, Ballerini L: ET(A)/ET(B) receptor antagonist bosentan inhibits neointimal development in collared carotid arteries of rabbits. Life Sci. 1998;63(18):PL259-66. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/9806221 # Richard V, Kaeffer N, Hogie M, Tron C, Blanc T, Thuillez C: Role of endogenous endothelin in myocardial and coronary endothelial injury after ischaemia and reperfusion in rats: studies with bosentan, a mixed ETA-ETB antagonist. Br J Pharmacol. 1994 Nov;113(3):869-76. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/7858879 # Said SA, Ammar el SM, Suddek GM: Effect of bosentan (ETA/ETB receptor antagonist) on metabolic changes during stress and diabetes. Pharmacol Res. 2005 Feb;51(2):107-15. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/15629255 unknown Endothelin B receptor Involved in endothelin receptor activity Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system EDNRB 13q22 Membrane; multi-pass membrane protein 102-126 138-163 176-197 219-243 272-296 325-350 363-389 9.05 49644.0 Human HUGO Gene Nomenclature Committee (HGNC) HGNC:3180 GenAtlas EDNRB GeneCards EDNRB GenBank Gene Database M74921 GenBank Protein Database 182276 IUPHAR 220 Guide to Pharmacology 21 UniProtKB P24530 UniProt Accession EDNRB_HUMAN Endothelin B receptor precursor Endothelin receptor Non- selective type ET-B >Endothelin B receptor precursor MQPPPSLCGRALVALVLACGLSRIWGEERGFPPDRATPLLQTAEIMTPPTKTLWPKGSNA SLARSLAPAEVPKGDRTAGSPPRTISPPPCQGPIEIKETFKYINTVVSCLVFVLGIIGNS TLLRIIYKNKCMRNGPNILIASLALGDLLHIVIDIPINVYKLLAEDWPFGAEMCKLVPFI QKASVGITVLSLCALSIDRYRAVASWSRIKGIGVPKWTAVEIVLIWVVSVVLAVPEAIGF DIITMDYKGSYLRICLLHPVQKTAFMQFYKTAKDWWLFSFYFCLPLAITAFFYTLMTCEM LRKKSGMQIALNDHLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTLYNQNDPNRCEL LSFLLVLDYIGINMASLNSCINPIALYLVSKRFKNCFKSCLCCWCQSFEEKQSLEEKQSC LKFKANDHGYDNFRSSNKYSSS >1329 bp ATGCAGCCGCCTCCAAGTCTGTGCGGACGCGCCCTGGTTGCGCTGGTTCTTGCCTGCGGC CTGTCGCGGATCTGGGGAGAGGAGAGAGGCTTCCCGCCTGACAGGGCCACTCCGCTTTTG CAAACCGCAGAGATAATGACGCCACCCACTAAGACCTTATGGCCCAAGGGTTCCAACGCC AGTCTGGCGCGGTCGTTGGCACCTGCGGAGGTGCCTAAAGGAGACAGGACGGCAGGATCT CCGCCACGCACCATCTCCCCTCCCCCGTGCCAAGGACCCATCGAGATCAAGGAGACTTTC AAATACATCAACACGGTTGTGTCCTGCCTTGTGTTCGTGCTGGGGATCATCGGGAACTCC ACACTTCTGAGAATTATCTACAAGAACAAGTGCATGCGAAACGGTCCCAATATCTTGATC GCCAGCTTGGCTCTGGGAGACCTGCTGCACATCGTCATTGACATCCCTATCAATGTCTAC AAGCTGCTGGCAGAGGACTGGCCATTTGGAGCTGAGATGTGTAAGCTGGTGCCTTTCATA CAGAAAGCCTCCGTGGGAATCACTGTGCTGAGTCTATGTGCTCTGAGTATTGACAGATAT CGAGCTGTTGCTTCTTGGAGTAGAATTAAAGGAATTGGGGTTCCAAAATGGACAGCAGTA GAAATTGTTTTGATTTGGGTGGTCTCTGTGGTTCTGGCTGTCCCTGAAGCCATAGGTTTT GATATAATTACGATGGACTACAAAGGAAGTTATCTGCGAATCTGCTTGCTTCATCCCGTT CAGAAGACAGCTTTCATGCAGTTTTACAAGACAGCAAAAGATTGGTGGCTGTTCAGTTTC TATTTCTGCTTGCCATTGGCCATCACTGCATTTTTTTATACACTAATGACCTGTGAAATG TTGAGAAAGAAAAGTGGCATGCAGATTGCTTTAAATGATCACCTAAAGCAGAGACGGGAA GTGGCCAAAACCGTCTTTTGCCTGGTCCTTGTCTTTGCCCTCTGCTGGCTTCCCCTTCAC CTCAGCAGGATTCTGAAGCTCACTCTTTATAATCAGAATGATCCCAATAGATGTGAACTT TTGAGCTTTCTGTTGGTATTGGACTATATTGGTATCAACATGGCTTCACTGAATTCCTGC ATTAACCCAATTGCTCTGTATTTGGTGAGCAAAAGATTCAAAAACTGCTTTAAGTCATGC TTATGCTGCTGGTGCCAGTCATTTGAAGAAAAACAGTCCTTGGAGGAAAAGCAGTCGTGC TTAAAGTTCAAAGCTAATGATCACGGATATGACAACTTCCGTTCCAGTAATAAATACAGC TCATCTTGA PF00001 7tm_1 component cell component intrinsic to membrane component integral to membrane component membrane function receptor activity function transmembrane receptor activity function G-protein coupled receptor activity function rhodopsin-like receptor activity function peptide receptor activity, G-protein coupled function signal transducer activity function endothelin receptor activity process cellular process process cell communication process signal transduction process cell surface receptor linked signal transduction process G-protein coupled receptor protein signaling pathway BE0002793 Cytochrome P450 2C9 Human substrate inhibitor # Pulido T, Sandoval J, Roquet I, Gutierrez R, Rueda T, Pena H, Santos E, Miranda MT, Lupi E: Interaction of acenocoumarol and sitaxentan in pulmonary arterial hypertension. Eur J Clin Invest. 2009 Jun;39 Suppl 2:14-8. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/19335742 # Opitz CF, Ewert R, Kirch W, Pittrow D: Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter? Eur Heart J. 2008 Aug;29(16):1936-48. Epub 2008 Jun 17. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/18562303 # Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarlin J: Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study. Chest. 2002 Jun;121(6):1860-8. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/12065350 unknown Cytochrome P450 2C9 Involved in monooxygenase activity 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 CYP2C9 10q24 Endoplasmic reticulum None 7.99 55629.0 Human HUGO Gene Nomenclature Committee (HGNC) HGNC:2623 GenAtlas CYP2C9 GenBank Gene Database AY341248 UniProtKB P11712 UniProt Accession CP2C9_HUMAN (R)-limonene 6-monooxygenase (S)- limonene 7-monooxygenase (S)-limonene 6-monooxygenase CYPIIC9 EC 1.14.13.48 EC 1.14.13.49 EC 1.14.13.80 P-450MP P450 MP-4/MP-8 P450 PB-1 S- mephenytoin 4-hydroxylase >Cytochrome P450 2C9 MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKV YGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKW KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS IIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFM KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTE TTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYID LLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK KSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP PFYQLCFIPV >1473 bp ATGGATTCTCTTGTGGTCCTTGTGCTCTGTCTCTCATGTTTGCTTCTCCTTTCACTCTGG AGACAGAGCTCTGGGAGAGGAAAACTCCCTCCTGGCCCCACTCCTCTCCCAGTGATTGGA AATATCCTACAGATAGGTATTAAGGACATCAGCAAATCCTTAACCAATCTCTCAAAGGTC TATGGCCCTGTGTTCACTCTGTATTTTGGCCTGAAACCCATAGTGGTGCTGCATGGATAT GAAGCAGTGAAGGAAGCCCTGATTGATCTTGGAGAGGAGTTTTCTGGAAGAGGCATTTTC CCACTGGCTGAAAGAGCTAACAGAGGATTTGGAATTGTTTTCAGCAATGGAAAGAAATGG AAGGAGATCCGGCGTTTCTCCCTCATGACGCTGCGGAATTTTGGGATGGGGAAGAGGAGC ATTGAGGACCGTGTTCAAGAGGAAGCCCGCTGCCTTGTGGAGGAGTTGAGAAAAACCAAG GCCTCACCCTGTGATCCCACTTTCATCCTGGGCTGTGCTCCCTGCAATGTGATCTGCTCC ATTATTTTCCATAAACGTTTTGATTATAAAGATCAGCAATTTCTTAACTTAATGGAAAAG TTGAATGAAAACATCAAGATTTTGAGCAGCCCCTGGATCCAGATCTGCAATAATTTTTCT CCTATCATTGATTACTTCCCGGGAACTCACAACAAATTACTTAAAAACGTTGCTTTTATG AAAAGTTATATTTTGGAAAAAGTAAAAGAACACCAAGAATCAATGGACATGAACAACCCT CAGGACTTTATTGATTGCTTCCTGATGAAAATGGAGAAGGAAAAGCACAACCAACCATCT GAATTTACTATTGAAAGCTTGGAAAACACTGCAGTTGACTTGTTTGGAGCTGGGACAGAG ACGACAAGCACAACCCTGAGATATGCTCTCCTTCTCCTGCTGAAGCACCCAGAGGTCACA GCTAAAGTCCAGGAAGAGATTGAACGTGTGATTGGCAGAAACCGGAGCCCCTGCATGCAA GACAGGAGCCACATGCCCTACACAGATGCTGTGGTGCACGAGGTCCAGAGATACATTGAC CTTCTCCCCACCAGCCTGCCCCATGCAGTGACCTGTGACATTAAATTCAGAAACTATCTC ATTCCCAAGGGCACAACCATATTAATTTCCCTGACTTCTGTGCTACATGACAACAAAGAA TTTCCCAACCCAGAGATGTTTGACCCTCATCACTTTCTGGATGAAGGTGGCAATTTTAAG AAAAGTAAATACTTCATGCCTTTCTCAGCAGGAAAACGGATTTGTGTGGGAGAAGCCCTG GCCGGCATGGAGCTGTTTTTATTCCTGACCTCCATTTTACAGAACTTTAACCTGAAATCT CTGGTTGACCCAAAGAACCTTGACACCACTCCAGTTGTCAATGGATTTGCCTCTGTGCCG CCCTTCTACCAGCTGTGCTTCATTCCTGTCTGA PF00067 p450 function cation binding function transition metal ion binding function iron ion binding function binding function tetrapyrrole binding function catalytic activity function heme binding function monooxygenase activity function oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen function oxidoreductase activity function ion binding process generation of precursor metabolites and energy process electron transport process physiological process process metabolism process cellular metabolism unknown unknown BE0002638 Cytochrome P450 3A4 Human inhibitor # Stavros F, Kramer WG, Wilkins MR: The effects of sitaxentan on sildenafil pharmacokinetics and pharmacodynamics in healthy subjects. Br J Clin Pharmacol. 2010 Jan;69(1):23-6. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/20078609 # Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarlin J: Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study. Chest. 2002 Jun;121(6):1860-8. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/12065350 unknown Cytochrome P450 3A4 Involved in monooxygenase activity 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 CYP3A4 7q21.1 Endoplasmic reticulum 2-22 8.25 57344.0 Human HUGO Gene Nomenclature Committee (HGNC) HGNC:2637 GenAtlas CYP3A4 GenBank Gene Database M18907 UniProtKB P08684 UniProt Accession CP3A4_HUMAN CYPIIIA4 EC 1.14.13.67 EC 1.14.13.97 NF-25 Nifedipine oxidase P450-PCN1 Quinine 3-monooxygenase Taurochenodeoxycholate 6-alpha- hydroxylase >Cytochrome P450 3A4 MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMF DMECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISI AEDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYS MDVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICV FPREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSI IFIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVV NETLRLFPIAMRLERVCKKDVEINGMFIPKGVVVMIPSYALHRDPKYWTEPEKFLPERFS KKNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLG GLLQPEKPVVLKVESRDGTVSGA >1512 bp ATGGCTCTCATCCCAGACTTGGCCATGGAAACCTGGCTTCTCCTGGCTGTCAGCCTGGTG CTCCTCTATCTATATGGAACCCATTCACATGGACTTTTTAAGAAGCTTGGAATTCCAGGG CCCACACCTCTGCCTTTTTTGGGAAATATTTTGTCCTACCATAAGGGCTTTTGTATGTTT GACATGGAATGTCATAAAAAGTATGGAAAAGTGTGGGGCTTTTATGATGGTCAACAGCCT GTGCTGGCTATCACAGATCCTGACATGATCAAAACAGTGCTAGTGAAAGAATGTTATTCT GTCTTCACAAACCGGAGGCCTTTTGGTCCAGTGGGATTTATGAAAAGTGCCATCTCTATA GCTGAGGATGAAGAATGGAAGAGATTACGATCATTGCTGTCTCCAACCTTCACCAGTGGA AAACTCAAGGAGATGGTCCCTATCATTGCCCAGTATGGAGATGTGTTGGTGAGAAATCTG AGGCGGGAAGCAGAGACAGGCAAGCCTGTCACCTTGAAAGACGTCTTTGGGGCCTACAGC ATGGATGTGATCACTAGCACATCATTTGGAGTGAACATCGACTCTCTCAACAATCCACAA GACCCCTTTGTGGAAAACACCAAGAAGCTTTTAAGATTTGATTTTTTGGATCCATTCTTT CTCTCAATAACAGTCTTTCCATTCCTCATCCCAATTCTTGAAGTATTAAATATCTGTGTG TTTCCAAGAGAAGTTACAAATTTTTTAAGAAAATCTGTAAAAAGGATGAAAGAAAGTCGC CTCGAAGATACACAAAAGCACCGAGTGGATTTCCTTCAGCTGATGATTGACTCTCAGAAT TCAAAAGAAACTGAGTCCCACAAAGCTCTGTCCGATCTGGAGCTCGTGGCCCAATCAATT ATCTTTATTTTTGCTGGCTATGAAACCACGAGCAGTGTTCTCTCCTTCATTATGTATGAA CTGGCCACTCACCCTGATGTCCAGCAGAAACTGCAGGAGGAAATTGATGCAGTTTTACCC AATAAGGCACCACCCACCTATGATACTGTGCTACAGATGGAGTATCTTGACATGGTGGTG AATGAAACGCTCAGATTATTCCCAATTGCTATGAGACTTGAGAGGGTCTGCAAAAAAGAT GTTGAGATCAATGGGATGTTCATTCCCAAAGGGGTGGTGGTGATGATTCCAAGCTATGCT CTTCACCGTGACCCAAAGTACTGGACAGAGCCTGAGAAGTTCCTCCCTGAAAGATTCAGC AAGAAGAACAAGGACAACATAGATCCTTACATATACACACCCTTTGGAAGTGGACCCAGA AACTGCATTGGCATGAGGTTTGCTCTCATGAACATGAAACTTGCTCTAATCAGAGTCCTT CAGAACTTCTCCTTCAAACCTTGTAAAGAAACACAGATCCCCCTGAAATTAAGCTTAGGA GGACTTCTTCAACCAGAAAAACCCGTTGTTCTAAAGGTTGAGTCAAGGGATGGCACCGTA AGTGGAGCCTGA PF00067 p450 function oxidoreductase activity function ion binding function cation binding function transition metal ion binding function iron ion binding function binding function tetrapyrrole binding function catalytic activity function heme binding function monooxygenase activity function oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen process generation of precursor metabolites and energy process electron transport process physiological process process metabolism process cellular metabolism unknown unknown BE0003536 Cytochrome P450 2C19 Human inhibitor # Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarlin J: Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study. Chest. 2002 Jun;121(6):1860-8. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/12065350 unknown Cytochrome P450 2C19 Secondary metabolites biosynthesis, transport and catabolism 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 CYP2C19 10q24.1-q24.3 Endoplasmic reticulum membrane None 7.42 55930.5 Human HUGO Gene Nomenclature Committee (HGNC) GNC:2621 GeneCards CYP2C19 GenBank Gene Database M61854 GenBank Protein Database 181344 UniProtKB P33261 UniProt Accession CP2CJ_HUMAN (R)-limonene 6-monooxygenase (S)-limonene 6-monooxygenase (S)-limonene 7-monooxygenase CYPIIC17 CYPIIC19 Mephenytoin 4-hydroxylase P450-11A P450-254C >Cytochrome P450 2C19 MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDVSKSLTNLSKI YGPVFTLYFGLERMVVLHGYEVVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKRW KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS IIFQKRFDYKDQQFLNLMEKLNENIRIVSTPWIQICNNFPTIIDYFPGTHNKLLKNLAFM ESDILEKVKEHQESMDINNPRDFIDCFLIKMEKEKQNQQSEFTIENLVITAADLLGAGTE TTSTTLRYALLLLLKHPEVTAKVQEEIERVVGRNRSPCMQDRGHMPYTDAVVHEVQRYID LIPTSLPHAVTCDVKFRNYLIPKGTTILTSLTSVLHDNKEFPNPEMFDPRHFLDEGGNFK KSNYFMPFSAGKRICVGEGLARMELFLFLTFILQNFNLKSLIDPKDLDTTPVVNGFASVP PFYQLCFIPV >1473 bp ATGGATCCTTTTGTGGTCCTTGTGCTCTGTCTCTCATGTTTGCTTCTCCTTTCAATCTGG AGACAGAGCTCTGGGAGAGGAAAACTCCCTCCTGGCCCCACTCCTCTCCCAGTGATTGGA AATATCCTACAGATAGATATTAAGGATGTCAGCAAATCCTTAACCAATCTCTCAAAAATC TATGGCCCTGTGTTCACTCTGTATTTTGGCCTGGAACGCATGGTGGTGCTGCATGGATAT GAAGTGGTGAAGGAAGCCCTGATTGATCTTGGAGAGGAGTTTTCTGGAAGAGGCCATTTC CCACTGGCTGAAAGAGCTAACAGAGGATTTGGAATCGTTTTCAGCAATGGAAAGAGATGG AAGGAGATCCGGCGTTTCTCCCTCATGACGCTGCGGAATTTTGGGATGGGGAAGAGGAGC ATTGAGGACCGTGTTCAAGAGGAAGCCCGCTGCCTTGTGGAGGAGTTGAGAAAAACCAAG GCTTCACCCTGTGATCCCACTTTCATCCTGGGCTGTGCTCCCTGCAATGTGATCTGCTCC ATTATTTTCCAGAAACGTTTCGATTATAAAGATCAGCAATTTCTTAACTTGATGGAAAAA TTGAATGAAAACATCAGGATTGTAAGCACCCCCTGGATCCAGATATGCAATAATTTTCCC ACTATCATTGATTATTTCCCGGGAACCCATAACAAATTACTTAAAAACCTTGCTTTTATG GAAAGTGATATTTTGGAGAAAGTAAAAGAACACCAAGAATCGATGGACATCAACAACCCT CGGGACTTTATTGATTGCTTCCTGATCAAAATGGAGAAGGAAAAGCAAAACCAACAGTCT GAATTCACTATTGAAAACTTGGTAATCACTGCAGCTGACTTACTTGGAGCTGGGACAGAG ACAACAAGCACAACCCTGAGATATGCTCTCCTTCTCCTGCTGAAGCACCCAGAGGTCACA GCTAAAGTCCAGGAAGAGATTGAACGTGTCATTGGCAGAAACCGGAGCCCCTGCATGCAG GACAGGGGCCACATGCCCTACACAGATGCTGTGGTGCACGAGGTCCAGAGATACATCGAC CTCATCCCCACCAGCCTGCCCCATGCAGTGACCTGTGACGTTAAATTCAGAAACTACCTC ATTCCCAAGGGCACAACCATATTAACTTCCCTCACTTCTGTGCTACATGACAACAAAGAA TTTCCCAACCCAGAGATGTTTGACCCTCGTCACTTTCTGGATGAAGGTGGAAATTTTAAG AAAAGTAACTACTTCATGCCTTTCTCAGCAGGAAAACGGATTTGTGTGGGAGAGGGCCTG GCCCGCATGGAGCTGTTTTTATTCCTGACCTTCATTTTACAGAACTTTAACCTGAAATCT CTGATTGACCCAAAGGACCTTGACACAACTCCTGTTGTCAATGGATTTGCTTCTGTCCCG CCCTTCTATCAGCTGTGCTTCATTCCTGTCTGA PF00067 p450 function catalytic activity function heme binding function monooxygenase activity function oxidoreductase activity function ion binding function cation binding function transition metal ion binding function iron ion binding function binding function tetrapyrrole binding process metabolism process cellular metabolism process generation of precursor metabolites and energy process electron transport process physiological process unknown unknown "

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