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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:03:42
Primary Accession Number DB00559
Secondary Accession Number
  • APRD00829
Name Bosentan
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description Bosentan is a dual endothelin receptor antagonist important in the treatment of pulmonary artery hypertension (PAH). It is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Tracleer®. Bosentan is used to treat pulmonary hypertension by blocking the action of endothelin molecules that would otherwise promote narrowing of the blood vessels and lead to high blood pressure.
Synonyms
  1. Bosentan hydrate
  2. bosentan
Brand Names
  1. Tracleer
Brand Mixtures Not Available
Chemical IUPAC Name 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide
Chemical Formula C27H29N5O6S
Chemical Structure Structure
CAS Registry Number 147536-97-8
InChI Identifier InChI=1/C27H29N5O6S/c1-27(2,3)18-10-12-19(13-11-18)39(34,35)32-23-22(38-21-9-6-5-8-20(21)36-4)26(37-17-16-33)31-25(30-23)24-28-14-7-15-29-24/h5-15,33H,16-17H2,1-4H3,(H,30,31,32)/f/h32H
InChI Key GJPICJJJRGTNOD-OKPOJWAQCQ
KEGG Drug D01227 Link Image
KEGG Compound Not Available
PubChem Compound 104865 Link Image
PubChem Substance 682323 Link Image
ChEBI ID Not Available
PharmGKB ID PA10034 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02244982 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/tracleer.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Bosentan Link Image
FDA Label
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 551.6140
Monoisotopic Molecular Weight 551.1839
State Solid
Melting Point Not Available
Experimental Water Solubility Poorly soluble in water (1.0 mg/100 ml) and in aqueous solutions at low pH (0.1 mg/100 ml at pH 1.1 and 4.0; 0.2 mg/100 ml at pH 5.0). Solubility increases at higher pH values (43 mg/100 ml at pH 7.5). Source: PhysProp
Predicted Water Solubility 9.04e-03 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 3.7 Source: PhysProp
Predicted LogP 4.18 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.79 Calculated using ALOGPS
Experimental Caco2 Permeability -5.98 [ADME Research, USCD]
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)N=C(N=C1OCCO)C1=NC=CC=N1
Canonical SMILES COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)N=C(N=C1OCCO)C1=NC=CC=N1
Drug Category
  • Antihypertensive Agents
ATC Codes
AHFS Codes
  • 92:00.00
Indication Used in the treatment of pulmonary arterial hypertension (PAH), to improve exercise ability and to decrease the rate of clinical worsening (in patients with WHO Class III or IV symptoms).
Pharmacology Bosentan 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. Bosentan blocks the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects.
Mechanism of Action Endothelin-1 (ET-1) is a neurohormone, the effects of which are mediated by binding to ETA and ETB receptors in the endothelium and vascular smooth muscle. ET-1 concentrations are elevated in plasma and lung tissue of patients with pulmonary arterial hypertension, suggesting a pathogenic role for ET-1 in this disease. Bosentan is a specific and competitive antagonist at endothelin receptor types ETA and ETB. Bosentan has a slightly higher affinity for ETA receptors than for ETB receptors.
Absorption Absolute bioavailability is approximately 50% and food does not affect absorption.
Toxicity Bosentan has been given as a single dose of up to 2400 mg in normal volunteers, or up to 2000 mg/day for 2 months in patients, without any major clinical consequences. The most common side effect was headache of mild to moderate intensity. In the cyclosporine A interaction study, in which doses of 500 and 1000 mg b.i.d. of bosentan were given concomitantly with cyclosporine A, trough plasma concentrations of bosentan increased 30-fold, resulting in severe headache, nausea, and vomiting, but no serious adverse events. Mild decreases in blood pressure and increases in heart rate were observed. There is no specific experience of overdosage with bosentan beyond the doses described above. Massive overdosage may result in pronounced hypotension requiring active cardiovascular support.
Protein Binding Greater than 98% to plasma proteins, mainly albumin.
Biotransformation Bosentan is metabolized in the liver by the cytochrome P450 enzymes CYP2C9 and CYP3A4 (and possibly CYP2C19), producing three metabolites, one of which, Ro 48-5033, is pharmacologically active and may contribute 10 to 20% to the total activity of the parent compound.
Half Life Terminal elimination half-life is about 5 hours in healthy adult subjects.
Dosage Forms
Form Route
Tablet Oral
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol Increases the anticoagulant effect
Anisindione Increases the anticoagulant effect
Atorvastatin Bosentan could decrease atorvastatin effect
Cerivastatin Bosentan could decrease the statin effect
Cyclosporine Cyclosporine increases the effect and toxicity of bosentan
Dicumarol Increase the anticoagulant effect
Ethinyl Estradiol Decreases the effect of contraceptive
Glibenclamide Increased risk of hepatic toxicity
Itraconazole This imidazole increases the effect and toxicity of bosentan
Ketoconazole This imidazole increases the effect and toxicity of bosentan
Lovastatin Bosentan could decrease the statin effect
Medroxyprogesterone Decreases the effect of contraceptive
Mestranol Decreases the effect of contraceptive
Norethindrone Decreases the effect of contraceptive
Simvastatin Bosentan could decrease the statin effect
Voriconazole This imidazole increases the effect and toxicity of bosentan
Warfarin Increases the anticoagulant effect
Food Interactions
  • Take without regard to meals.
Pathways Not Available
General References
  1. Wikipedia Link Image
  2. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A4 (CYP3A4)
  2. Cytochrome P450 2C9 (CYP2C9)
Targets
  1. Endothelin B receptor
  2. Endothelin-1 receptor
  3. Bile salt export pump
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 1 Gene Name CYP3A4
Enzyme 1 SwissProt ID P08684 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 2C9 (CYP2C9)
Enzyme 2 Gene Name CYP2C9
Enzyme 2 SwissProt ID P11712 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P11712|CP2C9_HUMAN Cytochrome P450 2C9 (EC 1.14.13.80) 
MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKV
YGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFM
KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYID
LLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK
KSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP
PFYQLCFIPV
Drug Target 1 [top]
Target 1 ID 49
Target 1 Name Endothelin B receptor
Target 1 Synonyms
  1. ET-B
  2. Endothelin B receptor precursor
  3. Endothelin receptor Non- selective type
Target 1 Gene Name EDNRB
Target 1 Protein Sequence >Endothelin B receptor precursor 
MQPPPSLCGRALVALVLACGLSRIWGEERGFPPDRATPLLQTAEIMTPPTKTLWPKGSNA
SLARSLAPAEVPKGDRTAGSPPRTISPPPCQGPIEIKETFKYINTVVSCLVFVLGIIGNS
TLLRIIYKNKCMRNGPNILIASLALGDLLHIVIDIPINVYKLLAEDWPFGAEMCKLVPFI
QKASVGITVLSLCALSIDRYRAVASWSRIKGIGVPKWTAVEIVLIWVVSVVLAVPEAIGF
DIITMDYKGSYLRICLLHPVQKTAFMQFYKTAKDWWLFSFYFCLPLAITAFFYTLMTCEM
LRKKSGMQIALNDHLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTLYNQNDPNRCEL
LSFLLVLDYIGINMASLNSCINPIALYLVSKRFKNCFKSCLCCWCQSFEEKQSLEEKQSC
LKFKANDHGYDNFRSSNKYSSS
Target 1 Number of Residues 449
Target 1 Molecular Weight 49644
Target 1 Theoretical pI 9.05
Target 1 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
peptide receptor activity, G-protein coupled
endothelin receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in endothelin receptor activity
Target 1 Specific Function 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
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-26
Target 1 Transmembrane Regions
  • 102-126
  • 138-163
  • 176-197
  • 219-243
  • 272-296
  • 325-350
  • 363-389
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 182276 Link Image
Target 1 UniProtKB/Swiss-Prot ID P24530 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name EDNRB_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >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
Target 1 GenBank Gene ID
Target 1 GeneCard ID EDNRB Link Image
Target 1 GenAtlas ID EDNRB Link Image
Target 1 HGNC ID HGNC:3180 Link Image
Target 1 Chromosome Location 13
Target 1 Locus 13q22
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Tsutsumi M, Liang G, Jones PA: Novel endothelin B receptor transcripts with the potential of generating a new receptor. Gene. 1999 Mar 4;228(1-2):43-9. [PubMed Link Image]
  2. Fuchs S, Amiel J, Claudel S, Lyonnet S, Corvol P, Pinet F: Functional characterization of three mutations of the endothelin B receptor gene in patients with Hirschsprung's disease: evidence for selective loss of Gi coupling. Mol Med. 2001 Feb;7(2):115-24. [PubMed Link Image]
  3. Verheij JB, Kunze J, Osinga J, van Essen AJ, Hofstra RM: ABCD syndrome is caused by a homozygous mutation in the EDNRB gene. Am J Med Genet. 2002 Mar 15;108(3):223-5. [PubMed Link Image]
  4. Pingault V, Girard M, Bondurand N, Dorkins H, Van Maldergem L, Mowat D, Shimotake T, Verma I, Baumann C, Goossens M: SOX10 mutations in chronic intestinal pseudo-obstruction suggest a complex physiopathological mechanism. Hum Genet. 2002 Aug;111(2):198-206. Epub 2002 Jul 6. [PubMed Link Image]
  5. Haendler B, Hechler U, Schleuning WD: Molecular cloning of human endothelin (ET) receptors ETA and ETB. J Cardiovasc Pharmacol. 1992;20 Suppl 12:S1-4. [PubMed Link Image]
  6. Arai H, Nakao K, Hosoda K, Ogawa Y, Nakagawa O, Komatsu Y, Imura H: [Molecular cloning of human endothelin receptors and their expression in vascular endothelial cells and smooth muscle cells] Jpn Circ J. 1992;56 Suppl 5:1303-7. [PubMed Link Image]
  7. Ogawa Y, Nakao K, Arai H, Nakagawa O, Hosoda K, Suga S, Nakanishi S, Imura H: Molecular cloning of a non-isopeptide-selective human endothelin receptor. Biochem Biophys Res Commun. 1991 Jul 15;178(1):248-55. [PubMed Link Image]
  8. Nakamuta M, Takayanagi R, Sakai Y, Sakamoto S, Hagiwara H, Mizuno T, Saito Y, Hirose S, Yamamoto M, Nawata H: Cloning and sequence analysis of a cDNA encoding human non-selective type of endothelin receptor. Biochem Biophys Res Commun. 1991 May 31;177(1):34-9. [PubMed Link Image]
  9. Sakamoto A, Yanagisawa M, Sakurai T, Takuwa Y, Yanagisawa H, Masaki T: Cloning and functional expression of human cDNA for the ETB endothelin receptor. Biochem Biophys Res Commun. 1991 Jul 31;178(2):656-63. [PubMed Link Image]
  10. Puffenberger EG, Hosoda K, Washington SS, Nakao K, deWit D, Yanagisawa M, Chakravart A: A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease. Cell. 1994 Dec 30;79(7):1257-66. [PubMed Link Image]
  11. 8429023 Arai H, Nakao K, Takaya K, Hosoda K, Ogawa Y, Nakanishi S, Imura H: The human endothelin-B receptor gene. Structural organization and chromosomal assignment. J Biol Chem. 1993 Feb 15;268(5):3463-70.
  12. 8440682 Elshourbagy NA, Korman DR, Wu HL, Sylvester DR, Lee JA, Nuthalaganti P, Bergsma DJ, Kumar CS, Nambi P: Molecular characterization and regulation of the human endothelin receptors. J Biol Chem. 1993 Feb 25;268(6):3873-9.
  13. 8630503 Hofstra RM, Osinga J, Tan-Sindhunata G, Wu Y, Kamsteeg EJ, Stulp RP, van Ravenswaaij-Arts C, Majoor-Krakauer D, Angrist M, Chakravarti A, Meijers C, Buys CH: A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome). Nat Genet. 1996 Apr;12(4):445-7.
  14. 8634719 Attie T, Till M, Pelet A, Amiel J, Edery P, Boutrand L, Munnich A, Lyonnet S: Mutation of the endothelin-receptor B gene in Waardenburg-Hirschsprung disease. Hum Mol Genet. 1995 Dec;4(12):2407-9.
  15. 8852659 Auricchio A, Casari G, Staiano A, Ballabio A: Endothelin-B receptor mutations in patients with isolated Hirschsprung disease from a non-inbred population. Hum Mol Genet. 1996 Mar;5(3):351-4.
  16. 8852660 Amiel J, Attie T, Jan D, Pelet A, Edery P, Bidaud C, Lacombe D, Tam P, Simeoni J, Flori E, Nihoul-Fekete C, Munnich A, Lyonnet S: Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease. Hum Mol Genet. 1996 Mar;5(3):355-7.
  17. 9261180 Okamoto Y, Ninomiya H, Tanioka M, Sakamoto A, Miwa S, Masaki T: Palmitoylation of human endothelinB. Its critical role in G protein coupling and a differential requirement for the cytoplasmic tail by G protein subtypes. J Biol Chem. 1997 Aug 22;272(34):21589-96.
  18. 9284755 Bourgeois C, Robert B, Rebourcet R, Mondon F, Mignot TM, Duc-Goiran P, Ferre F: Endothelin-1 and ETA receptor expression in vascular smooth muscle cells from human placenta: a new ETA receptor messenger ribonucleic acid is generated by alternative splicing of exon 3. J Clin Endocrinol Metab. 1997 Sep;82(9):3116-23.
  19. 9359036 Hofstra RM, Osinga J, Buys CH: Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype. Eur J Hum Genet. 1997 Jul-Aug;5(4):180-5.
  20. 9760196 Svensson PJ, Anvret M, Molander ML, Nordenskjold A: Phenotypic variation in a family with mutations in two Hirschsprung-related genes (RET and endothelin receptor B). Hum Genet. 1998 Aug;103(2):145-8.
Target 1 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  2. 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 Link Image]
  3. 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 Link Image]
  4. 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 Link Image]
  5. 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 Link Image]
  6. 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 Link Image]
Drug Target 2 [top]
Target 2 ID 578
Target 2 Name Endothelin-1 receptor
Target 2 Synonyms
  1. ET-A
  2. ETA-R
  3. Endothelin A receptor
  4. Endothelin-1 receptor precursor
  5. hET- AR
Target 2 Gene Name EDNRA
Target 2 Protein Sequence >Endothelin-1 receptor precursor 
METLCLRASFWLALVGCVISDNPERYSTNLSNHVDDFTTFRGTELSFLVTTHQPTNLVLP
SNGSMHNYCPQQTKITSAFKYINTVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIA
SLALGDLIYVVIDLPINVFKLLAGRWPFDHNDFGVFLCKLFPFLQKSSVGITVLNLCALS
VDRYRAVASWSRVQGIGIPLVTAIEIVSIWILSFILAIPEAIGFVMVPFEYRGEQHKTCM
LNATSKFMEFYQDVKDWWLFGFYFCMPLVCTAIFYTLMTCEMLNRRNGSLRIALSEHLKQ
RREVAKTVFCLVVIFALCWFPLHLSRILKKTVYNEMDKNRCELLSFLLLMDYIGINLATM
NSCINPIALYFVSKKFKNCFQSCLCCCCYQSKSLMTSVPMNGTSIQWKNHDQNNHNTDRS
SHKDSMN
Target 2 Number of Residues 434
Target 2 Molecular Weight 48723
Target 2 Theoretical pI 8.41
Target 2 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
peptide receptor activity, G-protein coupled
endothelin receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 2 General Function Involved in endothelin receptor activity
Target 2 Specific Function 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
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-20
Target 2 Transmembrane Regions
  • 81-102
  • 113-132
  • 160-181
  • 206-229
  • 257-278
  • 307-328
  • 348-372
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 238636 Link Image
Target 2 UniProtKB/Swiss-Prot ID P25101 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name EDNRA_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 2 Gene Sequence >1284 bp 
ATGGAAACCCTTTGCCTCAGGGCATCCTTTTGGCTGGCACTGGTTGGATGTGTAATCAGT
GATAATCCTGAGAGATACAGCACAAATCTAAGCAATCATGTGGATGATTTCACCACTTTT
CGTGGCACAGAGCTCAGCTTCCTGGTTACCACTCATCAACCCACTAATTTGGTCCTACCC
AGCAATGGCTCAATGCACAACTATTGCCCACAGCAGACTAAAATTACTTCAGCTTTCAAA
TACATTAACACTGTGATATCTTGTACTATTTTCATCGTGGGAATGGTGGGGAATGCAACT
CTGCTCAGGATCATTTACCAGAACAAATGTATGAGGAATGGCCCCAACGCGCTGATAGCC
AGTCTTGCCCTTGGAGACCTTATCTATGTGGTCATTGATCTCCCTATCAATGTATTTAAG
CTGCTGGCTGGGCGCTGGCCTTTTGATCACAATGACTTTGGCGTATTTCTTTGCAAGCTG
TTCCCCTTTTTGCAGAAGTCCTCGGTGGGGATCACCGTCCTCAACCTCTGCGCTCTTAGT
GTTGACAGGTACAGAGCAGTTGCCTCCTGGAGTCGTGTTCAGGGAATTGGGATTCCTTTG
GTAACTGCCATTGAAATTGTCTCCATCTGGATCCTGTCCTTTATCCTGGCCATTCCTGAA
GCGATTGGCTTCGTCATGGTACCCTTTGAATATAGGGGTGAACAGCATAAAACCTGTATG
CTCAATGCCACATCAAAATTCATGGAGTTCTACCAAGATGTAAAGGACTGGTGGCTCTTC
GGGTTCTATTTCTGTATGCCCTTGGTGTGCACTGCGATCTTCTACACCCTCATGACTTGT
GAGATGTTGAACAGAAGGAATGGCAGCTTGAGAATTGCCCTCAGTGAACATCTTAAGCAG
CGTCGAGAAGTGGCAAAAACAGTTTTCTGCTTGGTTGTAATTTTTGCTCTTTGCTGGTTC
CCTCTTCATTTAAGCCGTATATTGAAGAAAACTGTGTATAACGAGATGGACAAGAACCGA
TGTGAATTACTTAGTTTCTTACTGCTCATGGATTACATCGGTATTAACTTGGCAACCATG
AATTCATGTATAAACCCCATAGCTCTGTATTTTGTGAGCAAGAAATTTAAAAATTGTTTC
CAGTCATGCCTCTGCTGCTGCTGTTACCAGTCCAAAAGTCTGATGACCTCGGTCCCCATG
AACGGAACAAGCATCCAGTGGAAGAACCACGATCAAAACAACCACAACACAGACCGGAGC
AGCCATAAGGACAGCATGAACTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID EDNRA Link Image
Target 2 GenAtlas ID EDNRA Link Image
Target 2 HGNC ID HGNC:3179 Link Image
Target 2 Chromosome Location 4
Target 2 Locus 4q31.23
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Lee HJ, Chun M, Kandror KV: Tip60 and HDAC7 interact with the endothelin receptor a and may be involved in downstream signaling. J Biol Chem. 2001 May 18;276(20):16597-600. Epub 2001 Mar 21. [PubMed Link Image]
  2. Arai H, Nakao K, Hosoda K, Ogawa Y, Nakagawa O, Komatsu Y, Imura H: [Molecular cloning of human endothelin receptors and their expression in vascular endothelial cells and smooth muscle cells] Jpn Circ J. 1992;56 Suppl 5:1303-7. [PubMed Link Image]
  3. Hosoda K, Nakao K, Tamura N, Arai H, Ogawa Y, Suga S, Nakanishi S, Imura H: Organization, structure, chromosomal assignment, and expression of the gene encoding the human endothelin-A receptor. J Biol Chem. 1992 Sep 15;267(26):18797-804. [PubMed Link Image]
  4. Hayzer DJ, Rose PM, Lynch JS, Webb ML, Kienzle BK, Liu EC, Bogosian EA, Brinson E, Runge MS: Cloning and expression of a human endothelin receptor: subtype A. Am J Med Sci. 1992 Oct;304(4):231-8. [PubMed Link Image]
  5. Hosoda K, Nakao K, Hiroshi-Arai, Suga S, Ogawa Y, Mukoyama M, Shirakami G, Saito Y, Nakanishi S, Imura H: Cloning and expression of human endothelin-1 receptor cDNA. FEBS Lett. 1991 Aug 5;287(1-2):23-6. [PubMed Link Image]
  6. Cyr C, Huebner K, Druck T, Kris R: Cloning and chromosomal localization of a human endothelin ETA receptor. Biochem Biophys Res Commun. 1991 Nov 27;181(1):184-90. [PubMed Link Image]
  7. Adachi M, Yang YY, Furuichi Y, Miyamoto C: Cloning and characterization of cDNA encoding human A-type endothelin receptor. Biochem Biophys Res Commun. 1991 Nov 14;180(3):1265-72. [PubMed Link Image]
  8. Yang H, Tabuchi H, Furuichi Y, Miyamoto C: Molecular characterization of the 5'-flanking region of human genomic ETA gene. Biochem Biophys Res Commun. 1993 Jan 29;190(2):332-9. [PubMed Link Image]
  9. Elshourbagy NA, Korman DR, Wu HL, Sylvester DR, Lee JA, Nuthalaganti P, Bergsma DJ, Kumar CS, Nambi P: Molecular characterization and regulation of the human endothelin receptors. J Biol Chem. 1993 Feb 25;268(6):3873-9. [PubMed Link Image]
  10. Miyamoto Y, Yoshimasa T, Arai H, Takaya K, Ogawa Y, Itoh H, Nakao K: Alternative RNA splicing of the human endothelin-A receptor generates multiple transcripts. Biochem J. 1996 Feb 1;313 ( Pt 3):795-801. [PubMed Link Image]
  11. 9284755 Bourgeois C, Robert B, Rebourcet R, Mondon F, Mignot TM, Duc-Goiran P, Ferre F: Endothelin-1 and ETA receptor expression in vascular smooth muscle cells from human placenta: a new ETA receptor messenger ribonucleic acid is generated by alternative splicing of exon 3. J Clin Endocrinol Metab. 1997 Sep;82(9):3116-23.
Target 2 Drug References
  1. 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 Link Image]
  2. 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 Link Image]
  3. 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 Link Image]
  4. 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 Link Image]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  6. 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 Link Image]
Drug Target 3 [top]
Target 3 ID 776
Target 3 Name Bile salt export pump
Target 3 Synonyms
  1. ATP-binding cassette sub-family B member 11
Target 3 Gene Name ABCB11
Target 3 Protein Sequence >Bile salt export pump 
MSDSVILRSIKKFGEENDGFESDKSYNNDKKSRLQDEKKGDGVRVGFFQLFRFSSSTDIW
LMFVGSLCAFLHGIAQPGVLLIFGTMTDVFIDYDVELQELQIPGKACVNNTIVWTNSSLN
QNMTNGTRCGLLNIESEMIKFASYYAGIAVAVLITGYIQICFWVIAAARQIQKMRKFYFR
RIMRMEIGWFDCNSVGELNTRFSDDINKINDAIADQMALFIQRMTSTICGFLLGFFRGWK
LTLVIISVSPLIGIGAATIGLSVSKFTDYELKAYAKAGVVADEVISSMRTVAAFGGEKRE
VERYEKNLVFAQRWGIRKGIVMGFFTGFVWCLIFLCYAVAFWYGSTLVLDEGEYTPGTLV
QIFLSVIVGALNLGNASPCLEAFATGRAAATSIFETIDRKPIIDCMSEDGYKLDRIKGEI
EFHNVTFHYPSRPEVKILNDLNMVIKPGEMTALVGPSGAGKSTALQLIQRFYDPCEGMVT
VDGHDIRSLNIQWLRDQIGIVEQEPVLFSTTIAENIRYGREDATMEDIVQAAKEANAYNF
IMDLPQQFDTLVGEGGGQMSGGQKQRVAIARALIRNPKILLLDMATSALDNESEAMVQEV
LSKIQHGHTIISVAHRLSTVRAADTIIGFEHGTAVERGTHEELLERKGVYFTLVTLQSQG
NQALNEEDIKDATEDDMLARTFSRGSYQDSLRASIRQRSKSQLSYLVHEPPLAVVDHKST
YEEDRKDKDIPVQEEVEPAPVRRILKFSAPEWPYMLVGSVGAAVNGTVTPLYAFLFSQIL
GTFSIPDKEEQRSQINGVCLLFVAMGCVSLFTQFLQGYAFAKSGELLTKRLRKFGFRAML
GQDIAWFDDLRNSPGALTTRLATDASQVQGAAGSQIGMIVNSFTNVTVAMIIAFSFSWKL
SLVILCFFPFLALSGATQTRMLTGFASRDKQALEMVGQITNEALSNIRTVAGIGKERRFI
EALETELEKPFKTAIQKANIYGFCFAFAQCIMFIANSASYRYGGYLISNEGLHFSYVFRV
ISAVVLSATALGRAFSYTPSYAKAKISAARFFQLLDRQPPISVYNTAGEKWDNFQGKIDF
VDCKFTYPSRPDSQVLNGLSVSISPGQTLAFVGSSGCGKSTSIQLLERFYDPDQGKVMID
GHDSKKVNVQFLRSNIGIVSQEPVLFACSIMDNIKYGDNTKEIPMERVIAAAKQAQLHDF
VMSLPEKYETNVGSQGSQLSRGEKQRIAIARAIVRDPKILLLDEATSALDTESEKTVQVA
LDKAREGRTCIVIAHRLSTIQNADIIAVMAQGVVIEKGTHEELMAQKGAYYKLVTTGSPI
S
Target 3 Number of Residues 1343
Target 3 Molecular Weight 146395
Target 3 Theoretical pI 6.52
Target 3 GO Classification
Function
ATPase activity
hydrolase activity, acting on acid anhydrides, catalyzing transmembrane movement of substances
ATPase activity, coupled to transmembrane movement of substances
purine nucleotide binding
adenyl nucleotide binding
ATP binding
catalytic activity
hydrolase activity
hydrolase activity, acting on acid anhydrides
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides
pyrophosphatase activity
nucleoside-triphosphatase activity
binding
nucleotide binding
Process
physiological process
cellular physiological process
transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 3 General Function Defense mechanisms
Target 3 Specific Function Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • 63-83
  • 148-168
  • 216-236
  • 241-261
  • 320-340
  • 354-374
  • 756-776
  • 795-815
  • 870-890
  • 891-911
  • 980-1000
  • 1012-1032
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 3873243 Link Image
Target 3 UniProtKB/Swiss-Prot ID O95342 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name ABCBB_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 3 Gene Sequence >3966 bp 
ATGTCTGACTCAGTAATTCTTCGAAGTATAAAGAAATTTGGAGAGGAGAATGATGGTTTT
GAGTCAGATAAATCATATAATAATGATAAGAAATCAAGGTTACAAGATGAGAAGAAAGGT
GATGGCGTTAGAGTTGGCTTCTTTCAATTGTTTCGGTTTTCTTCATCAACTGACATTTGG
CTGATGTTTGTGGGAAGTTTGTGTGCATTTCTCCATGGAATAGCCCAGCCAGGCGTGCTA
CTCATTTTTGGCACAATGACAGATGTTTTTATTGACTACGACGTTGAGTTACAAGAACTC
CAGATTCCAGGAAAAGCATGTGTGAATAACACCATTGTATGGACTAACAGTTCCCTCAAC
CAGAACATGACAAATGGAACACGTTGTGGGTTGCTGAACATCGAGAGCGAAATGATCAAA
TTTGCCAGTTACTATGCTGGAATTGCTGTCGCAGTACTTATCACAGGATATATTCAAATA
TGCTTTTGGGTCATTGCCGCAGCTCGTCAGATACAGAAAATGAGAAAATTTTACTTTAGG
AGAATAATGAGAATGGAAATAGGGTGGTTTGACTGCAATTCAGTGGGGGAGCTGAATACA
AGATTCTCTGATGATATTAATAAAATCAATGATGCCATAGCTGACCAAATGGCCCTTTTC
ATTCAGCGCATGACCTCGACCATCTGTGGTTTCCTGTTGGGATTTTTCAGGGGTTGGAAA
CTGACCTTGGTTATTATTTCTGTCAGCCCTCTCATTGGGATTGGAGCAGCCACCATTGGT
CTGAGTGTGTCCAAGTTTACGGACTATGAGCTGAAGGCCTATGCCAAAGCAGGGGTGGTG
GCTGATGAAGTCATTTCATCAATGAGAACAGTGGCTGCTTTTGGTGGTGAGAAAAGAGAG
GTTGAAAGGTATGAGAAAAATCTTGTGTTCGCCCAGCGTTGGGGAATTAGAAAAGGAATA
GTGATGGGATTCTTTACTGGATTCGTGTGGTGTCTCATCTTTTTGTGTTATGCAGTGGCC
TTCTGGTACGGCTCCACACTTGTCCTGGATGAAGGAGAATATACACCAGGAACCCTTGTC
CAGATTTTCCTCAGTGTCATAGTAGGAGCTTTAAATCTTGGCAATGCCTCTCCTTGTTTG
GAAGCCTTTGCAACTGGACGTGCAGCAGCCACCAGCATTTTTGAGACAATAGACAGGAAA
CCCATCATTGACTGCATGTCAGAAGATGGTTACAAGTTGGATCGAATCAAGGGTGAAATT
GAATTCCATAATGTGACCTTCCATTATCCTTCCAGACCAGAGGTGAAGATTCTAAATGAC
CTCAACATGGTCATTAAACCAGGGGAAATGACAGCTCTGGTAGGACCCAGTGGAGCTGGA
AAAAGTACAGCACTGCAACTCATTCAGCGATTCTATGACCCCTGTGAAGGAATGGTGACC
GTGGATGGCCATGACATTCGCTCTCTTAACATTCAGTGGCTTAGAGATCAGATTGGGATA
GTGGAGCAAGAGCCAGTTCTGTTCTCTACCACCATTGCAGAAAATATTCGCTATGGCAGA
GAAGATGCAACAATGGAAGACATAGTCCAAGCTGCCAAGGAGGCCAATGCCTACAACTTC
ATCATGGACCTGCCACAGCAATTTGACACCCTTGTTGGAGAAGGAGGAGGCCAGATGAGT
GGTGGCCAGAAACAAAGGGTAGCTATCGCCAGAGCCCTCATCCGAAATCCCAAGATTCTG
CTTTTGGACATGGCCACCTCAGCTCTGGACAATGAGAGTGAAGCCATGGTGCAAGAAGTG
CTGAGTAAGATTCAGCATGGGCACACAATCATTTCAGTTGCTCATCGCTTGTCTACGGTC
AGAGCTGCAGATACCATCATTGGTTTTGAACATGGCACTGCAGTGGAAAGAGGGACCCAT
GAAGAATTACTGGAAAGGAAAGGTGTTTACTTCACTCTAGTGACTTTGCAAAGCCAGGGA
AATCAAGCTCTTAATGAAGAGGACATAAAGGATGCAACTGAAGATGACATGCTTGCGAGG
ACCTTTAGCAGAGGGAGCTACCAGGATAGTTTAAGGGCTTCCATCCGGCAACGCTCCAAG
TCTCAGCTTTCTTACCTGGTGCACGAACCTCCATTAGCTGTTGTAGATCATAAGTCTACC
TATGAAGAAGATAGAAAGGACAAGGACATTCCTGTGCAGGAAGAAGTTGAACCTGCCCCA
GTTAGGAGGATTCTGAAATTCAGTGCTCCAGAATGGCCCTACATGCTGGTAGGGTCTGTG
GGTGCAGCTGTGAACGGGACAGTCACACCCTTGTATGCCTTTTTATTCAGCCAGATTCTT
GGGACTTTTTCAATTCCTGATAAAGAGGAACAAAGGTCACAGATCAATGGTGTGTGCCTA
CTTTTTGTAGCAATGGGCTGTGTATCTCTTTTCACCCAATTTCTACAGGGATATGCCTTT
GCTAAATCTGGGGAGCTCCTAACAAAAAGGCTACGTAAATTTGGTTTCAGGGCAATGCTG
GGGCAAGATATTGCCTGGTTTGATGACCTCAGAAATAGCCCTGGAGCATTGACAACAAGA
CTTGCTACAGATGCTTCCCAAGTTCAAGGGGCTGCCGGCTCTCAGATCGGGATGATAGTC
AATTCCTTCACTAACGTCACTGTGGCCATGATCATTGCCTTCTCCTTTAGCTGGAAGCTG
AGCCTGGTCATCTTGTGCTTCTTCCCCTTCTTGGCTTTATCAGGAGCCACACAGACCAGG
ATGTTGACAGGATTTGCCTCTCGAGATAAGCAGGCCCTGGAGATGGTGGGACAGATTACA
AATGAAGCCCTCAGTAACATCCGCACTGTTGCTGGAATTGGAAAGGAGAGGCGGTTCATT
GAAGCACTTGAGACTGAGCTGGAGAAGCCCTTCAAGACAGCCATTCAGAAAGCCAATATT
TACGGATTCTGCTTTGCCTTTGCCCAGTGCATCATGTTTATTGCGAATTCTGCTTCCTAC
AGATATGGAGGTTACTTAATCTCCAATGAGGGGCTCCATTTCAGCTATGTGTTCAGGGTG
ATCTCTGCAGTTGTACTGAGTGCAACAGCTCTTGGAAGAGCCTTCTCTTACACCCCAAGT
TATGCAAAAGCTAAAATATCAGCTGCACGCTTTTTTCAACTGCTGGACCGACAACCCCCA
ATCAGTGTATACAATACTGCAGGTGAAAAATGGGACAACTTCCAGGGGAAGATTGATTTT
GTTGATTGTAAATTTACATATCCTTCTCGACCTGACTCGCAAGTTCTGAATGGTCTCTCA
GTGTCGATTAGTCCAGGGCAGACACTGGCGTTTGTTGGGAGCAGTGGATGTGGCAAAAGC
ACTAGCATTCAGCTGTTGGAACGTTTCTATGATCCTGATCAAGGGAAGGTGATGATAGAT
GGTCATGACAGCAAAAAAGTAAATGTCCAGTTCCTCCGCTCAAACATTGGAATTGTTTCC
CAGGAACCAGTGTTGTTTGCCTGTAGCATAATGGACAATATCAAGTATGGAGACAACACC
AAAGAAATTCCCATGGAAAGAGTCATAGCAGCTGCAAAACAGGCTCAGCTGCATGATTTT
GTCATGTCACTCCCAGAGAAATATGAAACTAACGTTGGGTCCCAGGGGTCTCAACTCTCT
AGAGGGGAGAAACAACGCATTGCTATTGCTCGGGCCATTGTACGAGATCCTAAAATCTTG
CTACTAGATGAAGCCACTTCTGCCTTAGACACAGAAAGTGAAAAGACGGTGCAGGTTGCT
CTAGACAAAGCCAGAGAGGGTCGGACCTGCATTGTCATTGCCCATCGCTTGTCCACCATC
CAGAACGCGGATATCATTGCTGTCATGGCACAGGGGGTGGTGATTGAAAAGGGGACCCAT
GAAGAACTGATGGCCCAAAAAGGAGCCTACTACAAACTAGTCACCACTGGATCCCCCATC
AGTTGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID ABCB11 Link Image
Target 3 GenAtlas ID ABCB11 Link Image
Target 3 HGNC ID HGNC:42 Link Image
Target 3 Chromosome Location 2
Target 3 Locus 2q24
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Chen HL, Chang PS, Hsu HC, Ni YH, Hsu HY, Lee JH, Jeng YM, Shau WY, Chang MH: FIC1 and BSEP defects in Taiwanese patients with chronic intrahepatic cholestasis with low gamma-glutamyltranspeptidase levels. J Pediatr. 2002 Jan;140(1):119-24. [PubMed Link Image]
  2. Saito S, Iida A, Sekine A, Miura Y, Ogawa C, Kawauchi S, Higuchi S, Nakamura Y: Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population. J Hum Genet. 2002;47(1):38-50. [PubMed Link Image]
  3. Strautnieks SS, Bull LN, Knisely AS, Kocoshis SA, Dahl N, Arnell H, Sokal E, Dahan K, Childs S, Ling V, Tanner MS, Kagalwalla AF, Nemeth A, Pawlowska J, Baker A, Mieli-Vergani G, Freimer NB, Gardiner RM, Thompson RJ: A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet. 1998 Nov;20(3):233-8. [PubMed Link Image]
Target 3 Drug References
  1. Fattinger K, Funk C, Pantze M, Weber C, Reichen J, Stieger B, Meier PJ: The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions. Clin Pharmacol Ther. 2001 Apr;69(4):223-31. [PubMed Link Image]
  2. Kemp DC, Brouwer KL: Viability assessment in sandwich-cultured rat hepatocytes after xenobiotic exposure. Toxicol In Vitro. 2004 Dec;18(6):869-77. [PubMed Link Image]
  3. Kemp DC, Zamek-Gliszczynski MJ, Brouwer KL: Xenobiotics inhibit hepatic uptake and biliary excretion of taurocholate in rat hepatocytes. Toxicol Sci. 2005 Feb;83(2):207-14. Epub 2004 Oct 27. [PubMed Link Image]
  4. Mano Y, Usui T, Kamimura H: Effects of bosentan, an endothelin receptor antagonist, on bile salt export pump and multidrug resistance-associated protein 2. Biopharm Drug Dispos. 2007 Jan;28(1):13-8. [PubMed Link Image]

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.