Target Information

Target General Infomation
Target ID
T23499
Former ID
TTDS00198
Target Name
Endothelin-1 receptor
Gene Name
EDNRA
Synonyms
ET-A; ETA receptor; ETA-R; Endothelin A receptor; Endothelin receptor A; HET-AR; EDNRA
Target Type
Successful
Disease Arrhythmia [ICD9: 427; ICD10: I47-I49]
Cerebrovascular disorders [ICD10: I60-I69]
Cardiovascular disorder [ICD10: I00-I99]
Diabetic nephropathy [ICD9: 250.4; ICD10: E11.21]
Hypotension [ICD9: 458, 796.3; ICD10: I95]
Heart disease [ICD9: 390-429; ICD10: I00-I52]
Hypertension [ICD9: 401; ICD10: I10-I16]
Hormone resistant prostate cancer [ICD9: 185; ICD10: C61]
Hormone refractory prostate cancer [ICD9: 140-229, 185; ICD10: C61]
Myocardial infarction [ICD9: 410; ICD10: I21, I22]
Nerve injury [ICD10: T14.4]
Pulmonary arterial hypertension [ICD9: 416; ICD10: I27.0, I27.2]
Pulmonary hypertension [ICD9: 416; ICD10: I27.0, I27.2]
Prostate cancer [ICD9: 185; ICD10: C61]
Premature labour [ICD9: 644, 765; ICD10: O60.1, P07.3]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Vasospasm following subarachnoid hemorrhage [ICD9: 430, 728.85, 852.0, 852.1; ICD10: I60, P10.3, R25.2, S06.6]
Unspecified [ICD code not available]
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.
BioChemical Class
GPCR rhodopsin
Target Validation
T23499
UniProt ID
P25101
Sequence
METLCLRASFWLALVGCVISDNPERYSTNLSNHVDDFTTFRGTELSFLVTTHQPTNLVLP
SNGSMHNYCPQQTKITSAFKYINTVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIA
SLALGDLIYVVIDLPINVFKLLAGRWPFDHNDFGVFLCKLFPFLQKSSVGITVLNLCALS
VDRYRAVASWSRVQGIGIPLVTAIEIVSIWILSFILAIPEAIGFVMVPFEYRGEQHKTCM
LNATSKFMEFYQDVKDWWLFGFYFCMPLVCTAIFYTLMTCEMLNRRNGSLRIALSEHLKQ
RREVAKTVFCLVVIFALCWFPLHLSRILKKTVYNEMDKNRCELLSFLLLMDYIGINLATM
NSCINPIALYFVSKKFKNCFQSCLCCCCYQSKSLMTSVPMNGTSIQWKNHDQNNHNTDRS
SHKDSMN
Drugs and Mode of Action
Drug(s) Ambrisentan Drug Info Approved Pulmonary arterial hypertension [1], [2]
Bosentan Drug Info Approved Pulmonary arterial hypertension [3], [4]
LU302146 Drug Info Approved Pulmonary hypertension [5], [6]
Macitentan Drug Info Approved Cardiovascular disorder [7], [8], [9]
Darusentan Drug Info Phase 3 Hypotension [10], [11]
PF-1228305 Drug Info Phase 3 Pulmonary hypertension [12]
BQ-123 Drug Info Phase 2 Pulmonary arterial hypertension [13], [14]
FR139317 Drug Info Phase 2 Hypertension [15], [16]
PD-145065 Drug Info Phase 2 Hypertension [17]
PS433540 Drug Info Phase 2 Hypertension [18]
sparsentan Drug Info Phase 2 Myocardial infarction [19]
TBC-3711 Drug Info Phase 2 Hypotension [20]
YM-598 Drug Info Phase 2 Prostate cancer [21]
ET-1 Drug Info Phase 0 Discovery agent [22], [23]
Atrasentan Drug Info Withdrawn from market Hormone refractory prostate cancer [24], [25]
Sitaxsentan Drug Info Withdrawn from market Pulmonary arterial hypertension [1], [26]
TBC 11251 (TBC) Drug Info Withdrawn from market Pulmonary arterial hypertension [27], [9]
Clazosentan Drug Info Discontinued in Phase 3 Vasospasm following subarachnoid hemorrhage [28]
Zibotentan Drug Info Discontinued in Phase 3 Hormone resistant prostate cancer [29], [30]
97-139 Drug Info Discontinued in Phase 2 Cerebrovascular disorders [31]
Avosentan Drug Info Discontinued in Phase 2 Diabetic nephropathy [32], [33]
BMS-193884 Drug Info Discontinued in Phase 2 Pulmonary arterial hypertension [34]
EDONENTAN HYDRATE Drug Info Discontinued in Phase 2 Pulmonary arterial hypertension [35]
ENRASENTAN Drug Info Discontinued in Phase 2 Pulmonary arterial hypertension [36]
J-104132 Drug Info Discontinued in Phase 2 Pulmonary arterial hypertension [37]
SB-209670 Drug Info Discontinued in Phase 2 Arrhythmia [38], [39]
A-216546 Drug Info Discontinued in Phase 1 Solid tumours [40]
SB-234551 Drug Info Discontinued in Phase 1 Nerve injury [41], [42]
ZD-1611 Drug Info Discontinued in Phase 1 Hypotension [43]
50-235 Drug Info Terminated Hypertension [44]
BMS-182874 Drug Info Terminated Hypertension [45]
BQ-518 Drug Info Terminated Hypertension [46]
BQ610 Drug Info Terminated Discovery agent [47]
MX-6120 Drug Info Terminated Heart disease [48]
PD-155080 Drug Info Terminated Hypertension [49]
PD142893 Drug Info Terminated Discovery agent [50]
PD156707 Drug Info Terminated Discovery agent [51], [52]
Inhibitor 2-HYDROXY-3,5-DIIODOBENZOIC ACID Drug Info [53]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one Drug Info [54]
Ac-bhg-F-N-Y-Y-W Drug Info [55]
Ac-w-F-F-N-Y-Y-W Drug Info [55]
Asterric acid Drug Info [56]
Bhg-F-N-Y-Y-W Drug Info [55]
BMS-182874 Drug Info [57]
Endothelin-2 Drug Info [58]
ET-1 Drug Info [58]
PD-163140 Drug Info [59]
Trp-Ile-Ile-Asp-Leu-Hisc(Cys-Ser-Val-Tyr-Phe-Cys) Drug Info [60]
Trp-Ile-Ile-Asp-Leu-Hisc(Cys-Val-Tyr-Phe-Cys) Drug Info [60]
W-F-F-N--Y-Y-W Drug Info [55]
Modulator 50-235 Drug Info [61]
BMS-187308 Drug Info
BMS-193884 Drug Info
Bosentan Drug Info [62]
BQ-518 Drug Info [63]
ENRASENTAN Drug Info [64]
J-104132 Drug Info [65]
Macitentan Drug Info [7]
PD-145065 Drug Info [17]
PD-155080 Drug Info
PS433540 Drug Info
SB-209670 Drug Info [66]
Antagonist 97-139 Drug Info [67], [9]
A-216546 Drug Info [68], [9]
Ambrisentan Drug Info [69]
Atrasentan Drug Info [70]
Avosentan Drug Info [71], [72]
BQ-123 Drug Info [73], [74]
BQ610 Drug Info [75]
Clazosentan Drug Info [76]
Darusentan Drug Info [77]
EDONENTAN HYDRATE Drug Info [78], [9]
FR139317 Drug Info [79]
HJP-272 Drug Info [80]
LU302146 Drug Info [81]
LU302872 Drug Info [81]
MX-6120 Drug Info [82]
PD142893 Drug Info [75]
PD156707 Drug Info [83]
PD164333 Drug Info [84]
PF-1228305 Drug Info [12]
SB-234551 Drug Info [85], [9]
Sitaxsentan Drug Info [1]
sparsentan Drug Info [86]
TBC 11251 (TBC) Drug Info [87]
TBC-3711 Drug Info [88]
YM-598 Drug Info [89]
ZD-1611 Drug Info [90]
Zibotentan Drug Info [91]
[125I]PD151242 Drug Info [92]
[125I]PD164333 Drug Info [84]
[3H]BQ123 Drug Info [93]
[3H]S0139 Drug Info [80]
Agonist sarafotoxin S6b Drug Info [94]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Calcium signaling pathway
cGMP-PKG signaling pathway
cAMP signaling pathway
Neuroactive ligand-receptor interaction
Vascular smooth muscle contraction
Renin secretion
Pathways in cancer
NetPath Pathway IL4 Signaling Pathway
PANTHER Pathway Endothelin signaling pathway
Pathway Interaction Database Endothelins
EGFR-dependent Endothelin signaling events
Reactome Peptide ligand-binding receptors
G alpha (q) signalling events
WikiPathways Prostaglandin Synthesis and Regulation
GPCRs, Class A Rhodopsin-like
Gastrin-CREB signalling pathway via PKC and MAPK
Peptide GPCRs
Endothelin Pathways
GPCR ligand binding
GPCR downstream signaling
GPCRs, Other
References
REF 1Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19.
REF 2(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3951).
REF 3Optimizing endothelin receptor antagonist use in the management of pulmonary arterial hypertension. Vasc Health Risk Manag. 2008;4(5):943-52.
REF 4(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3494).
REF 52007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
REF 6Ambrisentan, an endothelin receptor type A-selective endothelin receptor antagonist, for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother. 2009 Aug;10(11):1847-58.
REF 72013 FDA drug approvals. Nat Rev Drug Discov. 2014 Feb;13(2):85-9.
REF 8(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7352).
REF 9Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 10ClinicalTrials.gov (NCT00389779) DORADO-AC - Optimized Doses of Darusentan as Compared to an Active Control in Resistant Hypertension. U.S. National Institutes of Health.
REF 11(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3508).
REF 12Pfizer. Product Development Pipeline. March 31 2009.
REF 13ClinicalTrials.gov (NCT00586820) Role of Endothelin in Microvascular Dysfunction Following PCI for NSTEMI. U.S. National Institutes of Health.
REF 14(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 997).
REF 15(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 998).
REF 16Acute Endothelin-Receptor Inhibition Does Not Attenuate Acetylcholine-Induced Coronary Vasoconstriction in Experimental Hypercholesterolemia. Arteriosclerosis, Thrombosis, and Vascular Biology, 1998.18: 108-113.
REF 17Reversal of established responses to endothelin-1 in vivo and in vitro by the endothelin receptor antagonists, BQ-123 and PD 145065. Br J Pharmacol. 1994 May;112(1):207-13.
REF 18ClinicalTrials.gov (NCT00635232) A Study To Evaluate The Dose-Related Efficacy and Safety of PS433540 in Subjects With Hypertension. U.S. National Institutes of Health.
REF 19Dual angiotensin II and endothelin A receptor antagonists: synthesis of 2'-substituted N-3-isoxazolyl biphenylsulfonamides with improved potency and pharmacokinetics. J Med Chem. 2005 Jan 13;48(1):171-9.
REF 20ClinicalTrials.gov (NCT00272961) A Study Of Different Doses Of TBC3711 In Patients With Uncontrolled High Blood Pressure Already Taking Medications For High Blood Pressure.. U.S. National Institutes of Health.
REF 21ClinicalTrials.gov (NCT00050297) YM598 in Patients With Rising PSA After Initial Therapy for Localized Prostate Cancer. U.S. National Institutes of Health.
REF 22ClinicalTrials.gov (NCT02124824) Contribution of Endothelin-1 to Exercise Intolerance in Heart Failure. U.S. National Institutes of Health.
REF 23(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 989).
REF 24Current and future treatments of bone metastases. Expert Opin Emerg Drugs. 2008 Dec;13(4):609-27.
REF 25(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3487).
REF 26(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3950).
REF 27Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007312)
REF 28Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017374)
REF 29(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3539).
REF 30Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009560)
REF 31Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009311)
REF 32(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8260).
REF 33Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015393)
REF 34Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007870)
REF 35Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015788)
REF 36Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004637)
REF 37Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010566)
REF 38(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3528).
REF 39Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003996)
REF 40Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010699)
REF 41(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1000).
REF 42Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009010)
REF 43Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008908)
REF 44Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003913)
REF 45Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004811)
REF 46Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006825)
REF 47Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004314)
REF 48Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018158)
REF 49Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005553)
REF 50Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002573)
REF 51(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 999).
REF 52Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005545)
REF 53Allosteric inhibition of endothelin <span class="caps">ETA</span> receptors by 3, 5-dibromosalicylic acid. Mol Pharmacol. 2000 Dec;58(6):1461-9.
REF 54J Med Chem. 2010 Sep 9;53(17):6386-97.Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential.
REF 55Res-701-1, synthesis and a reevaluation of its effects on the endothelin receptors, Bioorg. Med. Chem. Lett. 5(6):621-626 (1995).
REF 56J Nat Prod. 2002 Jan;65(1):7-10.New chlorinated diphenyl ethers from an Aspergillus species.
REF 57J Med Chem. 2000 Aug 10;43(16):3111-7.Biphenylsulfonamide endothelin receptor antagonists. 2. Discovery of 4'-oxazolyl biphenylsulfonamides as a new class of potent, highly selective ET(A) antagonists.
REF 58J Nat Prod. 2009 Dec;72(12):2172-6.5-OHKF and NorKA, depsipeptides from a Hawaiian collection of Bryopsis pennata: binding properties for NorKA to the human neuropeptide Y Y1 receptor.
REF 59gamma-Carbamate butenolide analogues as potent ETA selective endothelin receptor antagonists and prodrugs, Bioorg. Med. Chem. Lett. 7(3):297-302 (1997).
REF 60Structure-activity relationships in a series of monocyclic endothelin analogues, Bioorg. Med. Chem. Lett. 4(4):567-572 (1994).
REF 61Structure-activity relationships of an endothelin ETA receptor antagonist, 50-235, and its derivatives. Eur J Pharmacol. 1993 Oct 15;247(2):219-21.
REF 62Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
REF 63Structure-activity relationships of cyclic pentapeptide endothelin A receptor antagonists. J Med Chem. 1995 Oct 13;38(21):4309-24.
REF 64Enrasentan, an antagonist of endothelin receptors. Cardiovasc Drug Rev. 2003 Spring;21(1):1-16.
REF 65Pharmacological properties of J-104132 (L-753,037), a potent, orally active, mixed ETA/ETB endothelin receptor antagonist. J Pharmacol Exp Ther. 1999 Jun;289(3):1262-70.
REF 66Effects of the endothelin receptor antagonist, SB 209670, on circulatory failure and organ injury in endotoxic shock in the anaesthetized rat. Br J Pharmacol. 1996 May;118(1):198-204.
REF 67S-0139 (Shionogi). Curr Opin Investig Drugs. 2002 Jul;3(7):1051-6.
REF 68Pharmacology of A-216546: a highly selective antagonist for endothelin ET(A) receptor. Eur J Pharmacol. 1999 Feb 5;366(2-3):189-201.
REF 69Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
REF 70Effects of a selective ET(A)-receptor antagonist, atrasentan (ABT-627), in murine models of allergic asthma: demonstration of mouse strain specificity. Clin Sci (Lond). 2002 Aug;103 Suppl 48:367S-370S.
REF 71Influence of avosentan (SPP3OI) on the pharmacokinetics of a second generation oral contraceptive containing ethinylestradiol and levonorgestrel in healthy female volunteers. Int J Clin Pharmacol Ther. 2006 Dec;44(12):668-74.
REF 72Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63.
REF 73The therapeutic potential of endothelin-1 receptor antagonists and endothelin-converting enzyme inhibitors on the cardiovascular system. Expert Opin Investig Drugs. 2002 Nov;11(11):1537-52.
REF 74Endothelin in heart failure: a promising therapeutic target? Heart. 1997 Feb;77(2):93-4.
REF 75Human optic nerve head astrocytes as a target for endothelin-1. Invest Ophthalmol Vis Sci. 2002 Aug;43(8):2704-13.
REF 76Effects of the selective endothelin A (ET(A)) receptor antagonist Clazosentan on cerebral perfusion and cerebral oxygenation following severe subarachnoid hemorrhage - preliminary results from a randomized clinical series. Acta Neurochir (Wien). 2007;149(9):911-8; discussion 918. Epub 2007 Aug 13.
REF 77Endothelin ETA receptor blockade with darusentan increases sodium and potassium excretion in aging rats. J Cardiovasc Pharmacol. 2006 Mar;47(3):456-62.
REF 78US patent application no. 9,062,094, Dipeptide-based prodrug linkers for aliphatic amine-containing drugs.
REF 79Reduction of bFGF-induced smooth muscle cell proliferation and endothelin receptor mRNA expression by mevastatin and atorvastatin. Biochem Pharmacol. 2002 Aug 1;64(3):497-505.
REF 80(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 219).
REF 81Influence of endothelin receptor antagonists on myocardial protein kinase C isoforms in uraemic cardiomyopathy. Clin Sci (Lond). 2002 Aug;103 Suppl 48:276S-279S.
REF 82Endothelin receptor antagonists in heart failure: current status and future directions. Drugs. 2004;64(10):1029-40.
REF 83Discovery and development of an endothelin A receptor-selective antagonist PD 156707. Pharm Biotechnol. 1998;11:81-112.
REF 84Characterization of [125I]-PD164333, an ETA selective non-peptide radiolabelled antagonist, in normal and diseased human tissues. Br J Pharmacol. 1998 Jan;123(2):223-30.
REF 85Effects of the novel selective endothelin ET(A) receptor antagonist, SB 234551, on the cardiovascular responses to endotoxaemia in conscious rats. Br J Pharmacol. 2001 Aug;133(8):1371-7.
REF 86J Med Chem. 2005 Oct 20;48(21):6523-43.Designed multiple ligands. An emerging drug discovery paradigm.
REF 87Systemic administration of the endothelin-A receptor antagonist TBC 11251 attenuates cerebral vasospasm after experimental subarachnoid hemorrhage: dose study and review of endothelin-based therapiesin the literature on cerebral vasospasm. Neurosurgery. 1998 Dec;43(6):1409-17; discussion 1417-8.
REF 88TBC3711, an ET(A) receptor antagonist, reduces neonatal hypoxia-induced pulmonary hypertension in piglets. Pediatr Res. 2001 Sep;50(3):374-83.
REF 89Role of the endothelin axis and its antagonists in the treatment of cancer. Br J Pharmacol. 2011 May; 163(2): 220-233.
REF 90Pharmacological profile of ZD1611, a novel, orally active endothelin ETA receptor antagonist. J Pharmacol Exp Ther. 1999 Sep;290(3):1085-91.
REF 91Clinical pipeline report, company report or official report of AstraZeneca (2009).
REF 92[125I]-PD151242: a selective radioligand for human ETA receptors. Br J Pharmacol. 1994 Jan;111(1):4-6.
REF 93[3H]BQ-123, a highly specific and reversible radioligand for the endothelin ETA receptor subtype. Eur J Pharmacol. 1995 Feb 14;274(1-3):1-6.
REF 94ETA receptor-mediated constrictor responses to endothelin peptides in human blood vessels in vitro. Br J Pharmacol. 1995 May;115(1):191-7.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.