Target Information
| Target General Information | Top | |||||
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| Target ID |
T92828
(Former ID: TTDS00199)
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| Target Name |
Endothelin B receptor (EDNRB)
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| Synonyms |
Endothelin receptor type B; Endothelin receptor Non-selective type; Endothelin receptor B; ETRB; ET-BR; ET-B
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| Gene Name |
EDNRB
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Cardiovascular disease [ICD-11: BA00-BE2Z] | |||||
| 2 | Pulmonary hypertension [ICD-11: BB01] | |||||
| Function |
Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Non-specific receptor for endothelin 1, 2, and 3.
Click to Show/Hide
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MQPPPSLCGRALVALVLACGLSRIWGEERGFPPDRATPLLQTAEIMTPPTKTLWPKGSNA
SLARSLAPAEVPKGDRTAGSPPRTISPPPCQGPIEIKETFKYINTVVSCLVFVLGIIGNS TLLRIIYKNKCMRNGPNILIASLALGDLLHIVIDIPINVYKLLAEDWPFGAEMCKLVPFI QKASVGITVLSLCALSIDRYRAVASWSRIKGIGVPKWTAVEIVLIWVVSVVLAVPEAIGF DIITMDYKGSYLRICLLHPVQKTAFMQFYKTAKDWWLFSFYFCLPLAITAFFYTLMTCEM LRKKSGMQIALNDHLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTLYNQNDPNRCEL LSFLLVLDYIGINMASLNSCINPIALYLVSKRFKNCFKSCLCCWCQSFEEKQSLEEKQSC LKFKANDHGYDNFRSSNKYSSS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T37YKZ | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | Bosentan | Drug Info | Approved | Pulmonary arterial hypertension | [2], [3] | |
| 2 | Macitentan | Drug Info | Approved | Cardiovascular disease | [1], [4], [5] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | BQ788 | Drug Info | Phase 3 | Acute kidney injury | [6] | |
| 2 | PD-145065 | Drug Info | Phase 2 | Hypertension | [7] | |
| 3 | SPI-1620 | Drug Info | Phase 2 | Solid tumour/cancer | [8], [9] | |
| Discontinued Drug(s) | [+] 3 Discontinued Drugs | + | ||||
| 1 | ENRASENTAN | Drug Info | Discontinued in Phase 2 | Pulmonary arterial hypertension | [10] | |
| 2 | J-104132 | Drug Info | Discontinued in Phase 2 | Pulmonary arterial hypertension | [11] | |
| 3 | SB-209670 | Drug Info | Discontinued in Phase 2 | Arrhythmia | [12], [13] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Modulator | [+] 7 Modulator drugs | + | ||||
| 1 | Bosentan | Drug Info | [14] | |||
| 2 | Macitentan | Drug Info | [1] | |||
| 3 | PD-145065 | Drug Info | [7] | |||
| 4 | ENRASENTAN | Drug Info | [18] | |||
| 5 | J-104132 | Drug Info | [19] | |||
| 6 | SB-209670 | Drug Info | [20], [21] | |||
| 7 | ENDG-4010 | Drug Info | [28] | |||
| Antagonist | [+] 6 Antagonist drugs | + | ||||
| 1 | BQ788 | Drug Info | [15] | |||
| 2 | PD142893 | Drug Info | [23] | |||
| 3 | A192621 | Drug Info | [25] | |||
| 4 | LU302872 | Drug Info | [30] | |||
| 5 | Ro 46-8443 | Drug Info | [28] | |||
| 6 | Sarafotoxin 6C | Drug Info | [23] | |||
| Agonist | [+] 3 Agonist drugs | + | ||||
| 1 | SPI-1620 | Drug Info | [16], [17] | |||
| 2 | BQ 3020 | Drug Info | [27] | |||
| 3 | [125I]IRL1620 | Drug Info | [28] | |||
| Inhibitor | [+] 15 Inhibitor drugs | + | ||||
| 1 | ET-1 | Drug Info | [22] | |||
| 2 | IRL-2500 | Drug Info | [22] | |||
| 3 | RES-701-1 | Drug Info | [24] | |||
| 4 | Ac-bhg-F-N-Y-Y-W | Drug Info | [26] | |||
| 5 | Ac-w-F-F-N-Y-Y-W | Drug Info | [26] | |||
| 6 | Bhg-F-N-Y-Y-W | Drug Info | [26] | |||
| 7 | Endothelin-3 | Drug Info | [29] | |||
| 8 | IRL-1722 | Drug Info | [22] | |||
| 9 | IRL-1841 | Drug Info | [22] | |||
| 10 | Linear peptide of RES-701-1 | Drug Info | [24] | |||
| 11 | PD-163140 | Drug Info | [31] | |||
| 12 | RES-701-1-C-terminal analogue | Drug Info | [32] | |||
| 13 | Trp-Ile-Ile-Asp-Leu-Hisc(Cys-Ser-Val-Tyr-Phe-Cys) | Drug Info | [33] | |||
| 14 | Trp-Ile-Ile-Asp-Leu-Hisc(Cys-Val-Tyr-Phe-Cys) | Drug Info | [33] | |||
| 15 | W-F-F-N--Y-Y-W | Drug Info | [26] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
| 1 | Calcium signaling pathway | |||||
| 2 | cGMP-PKG signaling pathway | |||||
| 3 | Neuroactive ligand-receptor interaction | |||||
| 4 | Melanogenesis | |||||
| 5 | Pathways in cancer | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | Endothelin signaling pathway | |||||
| PID Pathway | [+] 2 PID Pathways | + | ||||
| 1 | Endothelins | |||||
| 2 | Arf6 trafficking events | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Peptide ligand-binding receptors | |||||
| 2 | G alpha (q) signalling events | |||||
| WikiPathways | [+] 7 WikiPathways | + | ||||
| 1 | Prostaglandin Synthesis and Regulation | |||||
| 2 | GPCRs, Class A Rhodopsin-like | |||||
| 3 | Gastrin-CREB signalling pathway via PKC and MAPK | |||||
| 4 | Peptide GPCRs | |||||
| 5 | Endothelin Pathways | |||||
| 6 | GPCR ligand binding | |||||
| 7 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651. | |||||
| REF 2 | URL: 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 3 | Optimizing endothelin receptor antagonist use in the management of pulmonary arterial hypertension. Vasc Health Risk Manag. 2008;4(5):943-52. | |||||
| REF 4 | URL: 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 5 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 6 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 7 | Reversal 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 8 | URL: 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 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003990) | |||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004637) | |||||
| REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010566) | |||||
| REF 12 | URL: 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 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003996) | |||||
| REF 14 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 15 | BQ788, an endothelin ET(B) receptor antagonist, attenuates stab wound injury-induced reactive astrocytes in rat brain. Glia. 1999 May;26(3):268-71. | |||||
| REF 16 | Clinical pipeline report, company report or official report of Spectrum Phamaceuticals (2009). | |||||
| REF 17 | The 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 18 | Enrasentan, an antagonist of endothelin receptors. Cardiovasc Drug Rev. 2003 Spring;21(1):1-16. | |||||
| REF 19 | Pharmacological 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 20 | Effects 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 21 | Nonpeptide endothelin receptor antagonists. III. Effect of SB 209670 and BQ123 on acute renal failure in anesthetized dogs. J Pharmacol Exp Ther. 1994 Nov;271(2):769-75. | |||||
| REF 22 | IRL 2500: A potent ETB selective endothelin antagonist, Bioorg. Med. Chem. Lett. 6(19):2323-2328 (1996). | |||||
| REF 23 | Human optic nerve head astrocytes as a target for endothelin-1. Invest Ophthalmol Vis Sci. 2002 Aug;43(8):2704-13. | |||||
| REF 24 | RES-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 25 | Pyrrolidine-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 26 | Res-701-1, synthesis and a reevaluation of its effects on the endothelin receptors, Bioorg. Med. Chem. Lett. 5(6):621-626 (1995). | |||||
| REF 27 | Pharmacological differences between rat and human endothelin B receptors. Biochem Biophys Res Commun. 1995 Apr 17;209(2):506-12. | |||||
| REF 28 | URL: 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 29 | 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... J Med Chem. 2008 Nov 27;51(22):7094-8. | |||||
| REF 30 | Influence of endothelin receptor antagonists on myocardial protein kinase C isoforms in uraemic cardiomyopathy. Clin Sci (Lond). 2002 Aug;103 Suppl 48:276S-279S. | |||||
| REF 31 | gamma-Carbamate butenolide analogues as potent ETA selective endothelin receptor antagonists and prodrugs, Bioorg. Med. Chem. Lett. 7(3):297-302 (1997). | |||||
| REF 32 | Analogs of an endothelin antagonist RES-701-1: substitutions of C-terminal amino acid, Bioorg. Med. Chem. Lett. 6(7):775-778 (1996). | |||||
| REF 33 | Structure-activity relationships in a series of monocyclic endothelin analogues, Bioorg. Med. Chem. Lett. 4(4):567-572 (1994). | |||||
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