Target Information

Target General Infomation
Target ID
T92828
Former ID
TTDS00199
Target Name
Endothelin B receptor
Gene Name
EDNRB
Synonyms
ET-B; Endothelin receptor B; Endothelin receptor Non-selective type; EDNRB
Target Type
Successful
Disease Arrhythmia [ICD9: 427; ICD10: I47-I49]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Cardiovascular disorder [ICD10: I00-I99]
Hypertension [ICD9: 401; ICD10: I10-I16]
Pulmonary arterial hypertension [ICD9: 416; ICD10: I27.0, I27.2]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
Non-specific receptor for endothelin 1, 2, and3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
BioChemical Class
GPCR rhodopsin
Target Validation
T92828
UniProt ID
P24530
Sequence
MQPPPSLCGRALVALVLACGLSRIWGEERGFPPDRATPLLQTAEIMTPPTKTLWPKGSNA
SLARSLAPAEVPKGDRTAGSPPRTISPPPCQGPIEIKETFKYINTVVSCLVFVLGIIGNS
TLLRIIYKNKCMRNGPNILIASLALGDLLHIVIDIPINVYKLLAEDWPFGAEMCKLVPFI
QKASVGITVLSLCALSIDRYRAVASWSRIKGIGVPKWTAVEIVLIWVVSVVLAVPEAIGF
DIITMDYKGSYLRICLLHPVQKTAFMQFYKTAKDWWLFSFYFCLPLAITAFFYTLMTCEM
LRKKSGMQIALNDHLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTLYNQNDPNRCEL
LSFLLVLDYIGINMASLNSCINPIALYLVSKRFKNCFKSCLCCWCQSFEEKQSLEEKQSC
LKFKANDHGYDNFRSSNKYSSS
Drugs and Mode of Action
Drug(s) Bosentan Drug Info Approved Pulmonary arterial hypertension [1], [2]
Macitentan Drug Info Approved Cardiovascular disorder [3], [4], [5]
PD-145065 Drug Info Phase 2 Hypertension [6]
SPI-1620 Drug Info Phase 2 Cancer [7], [8]
BQ788 Drug Info Phase 1 Hypertension [9], [10]
ET-1 Drug Info Phase 0 Discovery agent [11], [12]
ENRASENTAN Drug Info Discontinued in Phase 2 Pulmonary arterial hypertension [13]
J-104132 Drug Info Discontinued in Phase 2 Pulmonary arterial hypertension [14]
SB-209670 Drug Info Discontinued in Phase 2 Arrhythmia [15], [16]
IRL-2500 Drug Info Terminated Discovery agent [17], [18]
PD142893 Drug Info Terminated Discovery agent [19]
RES-701-1 Drug Info Terminated Discovery agent [20], [21]
Antagonist A192621 Drug Info [22]
BQ788 Drug Info [23]
LU302872 Drug Info [24]
PD142893 Drug Info [25]
Ro 46-8443 Drug Info [26]
Sarafotoxin 6C Drug Info [25]
Inhibitor Ac-bhg-F-N-Y-Y-W Drug Info [27]
Ac-w-F-F-N-Y-Y-W Drug Info [27]
Bhg-F-N-Y-Y-W Drug Info [27]
Compound ET-3 Drug Info [28]
Compound RES-701-1(1-10)/[A15]ET-1 Drug Info [28]
Compound RES-701-1(1-10)/[A15]ET-3 Drug Info [28]
Compound RES-701-1(1-10)/[A15]SRTX6b Drug Info [28]
Compound SRTX6b Drug Info [28]
Compound [S15]ET-1 Drug Info [28]
Endothelin-3 Drug Info [29]
ET-1 Drug Info [30]
IRL-1722 Drug Info [30]
IRL-1841 Drug Info [30]
IRL-2500 Drug Info [30]
Linear peptide of RES-701-1 Drug Info [28]
PD-163140 Drug Info [31]
RES-701-1 Drug Info [28]
RES-701-1-C-terminal analogue Drug Info [32]
Trp-Ile-Ile-Asp-Leu-Hisc(Cys-Ser-Val-Tyr-Phe-Cys) Drug Info [33]
Trp-Ile-Ile-Asp-Leu-Hisc(Cys-Val-Tyr-Phe-Cys) Drug Info [33]
W-F-F-N--Y-Y-W Drug Info [27]
Modulator Bosentan Drug Info [34]
ENDG-4010 Drug Info [26]
ENRASENTAN Drug Info [35]
J-104132 Drug Info [36]
Macitentan Drug Info [3]
PD-145065 Drug Info [6]
SB-209670 Drug Info [37]
Agonist BQ 3020 Drug Info [38]
SPI-1620 Drug Info [39], [40]
[125I]IRL1620 Drug Info [26]
Pathways
KEGG Pathway Calcium signaling pathway
cGMP-PKG signaling pathway
Neuroactive ligand-receptor interaction
Melanogenesis
Pathways in cancer
PANTHER Pathway Endothelin signaling pathway
Pathway Interaction Database Endothelins
Arf6 trafficking 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
References
REF 1Optimizing endothelin receptor antagonist use in the management of pulmonary arterial hypertension. Vasc Health Risk Manag. 2008;4(5):943-52.
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: 3494).
REF 32013 FDA drug approvals. Nat Rev Drug Discov. 2014 Feb;13(2):85-9.
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: 7352).
REF 5Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 6Reversal 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 7(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: 3886).
REF 8Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003990)
REF 9ClinicalTrials.gov (NCT00427232) Endothelin-Receptor Blockade in Coronary Heart Disease. U.S. National Institutes of Health.
REF 10(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: 1010).
REF 11ClinicalTrials.gov (NCT02124824) Contribution of Endothelin-1 to Exercise Intolerance in Heart Failure. U.S. National Institutes of Health.
REF 12(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 13Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004637)
REF 14Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010566)
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: 3528).
REF 16Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003996)
REF 17(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: 3887).
REF 18Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006320)
REF 19Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002573)
REF 20(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: 3911).
REF 21Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007396)
REF 22Pyrrolidine-3-carboxylic acids as endothelin antagonists. 4. Side chain conformational restriction leads to ET(B) selectivity. J Med Chem. 1999 Sep 9;42(18):3668-78.
REF 23BQ788, an endothelin ET(B) receptor antagonist, attenuates stab wound injury-induced reactive astrocytes in rat brain. Glia. 1999 May;26(3):268-71.
REF 24Influence of endothelin receptor antagonists on myocardial protein kinase C isoforms in uraemic cardiomyopathy. Clin Sci (Lond). 2002 Aug;103 Suppl 48:276S-279S.
REF 25Human optic nerve head astrocytes as a target for endothelin-1. Invest Ophthalmol Vis Sci. 2002 Aug;43(8):2704-13.
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. (Target id: 220).
REF 27Res-701-1, synthesis and a reevaluation of its effects on the endothelin receptors, Bioorg. Med. Chem. Lett. 5(6):621-626 (1995).
REF 28RES-701-1/endothelin-1 hybrid peptide having a potent binding activity for type B receptor, Bioorg. Med. Chem. Lett. 7(13):1715-1720 (1997).
REF 29J Med Chem. 2008 Nov 27;51(22):7094-8.cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia.
REF 30IRL 2500: A potent ETB selective endothelin antagonist, Bioorg. Med. Chem. Lett. 6(19):2323-2328 (1996).
REF 31gamma-Carbamate butenolide analogues as potent ETA selective endothelin receptor antagonists and prodrugs, Bioorg. Med. Chem. Lett. 7(3):297-302 (1997).
REF 32Analogs of an endothelin antagonist RES-701-1: substitutions of C-terminal amino acid, Bioorg. Med. Chem. Lett. 6(7):775-778 (1996).
REF 33Structure-activity relationships in a series of monocyclic endothelin analogues, Bioorg. Med. Chem. Lett. 4(4):567-572 (1994).
REF 34Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
REF 35Enrasentan, an antagonist of endothelin receptors. Cardiovasc Drug Rev. 2003 Spring;21(1):1-16.
REF 36Pharmacological 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 37Effects 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 38Pharmacological differences between rat and human endothelin B receptors. Biochem Biophys Res Commun. 1995 Apr 17;209(2):506-12.
REF 39The efficacy and tolerability of two novel H(1)/H(3) receptor antagonists in seasonal allergic rhinitis. Int Arch Allergy Immunol. 2012;158(1):84-98.
REF 40Clinical pipeline report, company report or official report of Spectrum Phamaceuticals (2009).

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