Target Information
| Target General Information | Top | |||||
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| Target ID |
T15497
(Former ID: TTDR00673)
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| Target Name |
Prostaglandin E2 receptor EP1 (PTGER1)
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| Synonyms |
Prostanoid EP1 receptor; Prostaglandin E2 receptor EP1 subtype; PGE2 receptor EP1 subtype; PGE receptor, EP1 subtype; PGE receptor EP1 subtype; EP1 receptor
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| Gene Name |
PTGER1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Thrombosis [ICD-11: DB61-GB90] | |||||
| Function |
The activity of this receptor is mediated by G(q) proteins which activate a phosphatidylinositol-calcium second messenger system. May play a role as an important modulator of renal function. Implicated the smooth muscle contractile response to PGE2 in various tissues. Receptor for prostaglandin E2 (PGE2).
Click to Show/Hide
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MSPCGPLNLSLAGEATTCAAPWVPNTSAVPPSGASPALPIFSMTLGAVSNLLALALLAQA
AGRLRRRRSAATFLLFVASLLATDLAGHVIPGALVLRLYTAGRAPAGGACHFLGGCMVFF GLCPLLLGCGMAVERCVGVTRPLLHAARVSVARARLALAAVAAVALAVALLPLARVGRYE LQYPGTWCFIGLGPPGGWRQALLAGLFASLGLVALLAALVCNTLSGLALLRARWRRRSRR PPPASGPDSRRRWGAHGPRSASASSASSIASASTFFGGSRSSGSARRARAHDVEMVGQLV GIMVVSCICWSPMLVLVALAVGGWSSTSLQRPLFLAVRLASWNQILDPWVYILLRQAVLR QLLRLLPPRAGAKGGPAGLGLTPSAWEASSLRSSRHSGLSHF Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | AS-013 | Drug Info | Phase 3 | Thrombosis | [2] | |
| 2 | PGF2alpha | Drug Info | Clinical trial | Solid tumour/cancer | [3] | |
| Discontinued Drug(s) | [+] 3 Discontinued Drugs | + | ||||
| 1 | ZD6416 | Drug Info | Discontinued in Phase 2 | Pain | [4] | |
| 2 | ONO-8130 | Drug Info | Terminated | Pollakiuria | [5] | |
| 3 | ONO-8711 | Drug Info | Terminated | Pain | [6], [7] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Agonist | [+] 11 Agonist drugs | + | ||||
| 1 | AS-013 | Drug Info | [2] | |||
| 2 | PGF2alpha | Drug Info | [8] | |||
| 3 | 17-phenyl-omega-trinor-PGE2 | Drug Info | [8] | |||
| 4 | carbacyclin | Drug Info | [13] | |||
| 5 | cicaprost | Drug Info | [13] | |||
| 6 | cloprostenol | Drug Info | [14] | |||
| 7 | M&B 28767 | Drug Info | [16] | |||
| 8 | ONO-DI-004 | Drug Info | [19] | |||
| 9 | PGD2 | Drug Info | [14] | |||
| 10 | U46619 | Drug Info | [8] | |||
| 11 | ZK110841 | Drug Info | [14] | |||
| Antagonist | [+] 8 Antagonist drugs | + | ||||
| 1 | BUTAPROST | Drug Info | [1] | |||
| 2 | ZD6416 | Drug Info | [9] | |||
| 3 | ONO-8711 | Drug Info | [11], [12] | |||
| 4 | AH6809 | Drug Info | [8] | |||
| 5 | GW848687X | Drug Info | [15] | |||
| 6 | MF266-1 | Drug Info | [17] | |||
| 7 | ONO-8713 | Drug Info | [18] | |||
| 8 | SC-19220 | Drug Info | [8] | |||
| Modulator | [+] 3 Modulator drugs | + | ||||
| 1 | ONO-8130 | Drug Info | [10] | |||
| 2 | SC-51322 | Drug Info | [20] | |||
| 3 | ZM 325802 | Drug Info | [21] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Calcium signaling pathway | hsa04020 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.86E-01 | Radiality | 1.31E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 5.20E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| 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 | |||||
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| 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 | [+] 3 KEGG Pathways | + | ||||
| 1 | Calcium signaling pathway | |||||
| 2 | Neuroactive ligand-receptor interaction | |||||
| 3 | Pathways in cancer | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | PI3 kinase pathway | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Prostanoid ligand receptors | |||||
| 2 | G alpha (q) signalling events | |||||
| WikiPathways | [+] 6 WikiPathways | + | ||||
| 1 | Prostaglandin Synthesis and Regulation | |||||
| 2 | GPCRs, Class A Rhodopsin-like | |||||
| 3 | Gastrin-CREB signalling pathway via PKC and MAPK | |||||
| 4 | Small Ligand GPCRs | |||||
| 5 | GPCR ligand binding | |||||
| 6 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Evaluation of WO 2012/177618 A1 and US-2014/0179750 A1: novel small molecule antagonists of prostaglandin-E2 receptor EP2.Expert Opin Ther Pat. 2015 Jul;25(7):837-44. | |||||
| REF 2 | Effect of lipo-pro-prostaglandin E1, AS-013 on rat inner ear microcirculatory thrombosis. Prostaglandins Leukot Essent Fatty Acids. 1998 Sep;59(3):203-7. | |||||
| REF 3 | Stereocontrolled organocatalytic synthesis of prostaglandin PGF2alpha in seven steps. Nature. 2012 Sep 13;489(7415):278-81. | |||||
| REF 4 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009543) | |||||
| REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018852) | |||||
| REF 6 | 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: 1920). | |||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014044) | |||||
| REF 8 | Molecular cloning and characterization of the four rat prostaglandin E2 prostanoid receptor subtypes. Eur J Pharmacol. 1997 Dec 11;340(2-3):227-41. | |||||
| REF 9 | The prostaglandin E2 receptor-1 (EP-1) mediates acid-induced visceral pain hypersensitivity in humans. Gastroenterology. 2003 Jan;124(1):18-25. | |||||
| REF 10 | ONO-8130, a selective prostanoid EP1 receptor antagonist, relieves bladder pain in mice with cyclophosphamide-induced cystitis. Pain. 2011 Jun;152(6):1373-81. | |||||
| REF 11 | Chemopreventive effects of ONO-8711, a selective prostaglandin E receptor EP(1) antagonist, on breast cancer development. Carcinogenesis. 2001 Dec;22(12):2001-4. | |||||
| REF 12 | Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36. | |||||
| REF 13 | The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta. 2000 Jan 17;1483(2):285-93. | |||||
| REF 14 | Cloned human EP1 prostanoid receptor pharmacology characterized using radioligand binding techniques. J Pharm Pharmacol. 2002 Apr;54(4):539-47. | |||||
| REF 15 | The discovery of 6-[2-(5-chloro-2-{[(2,4-difluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylic acid, GW848687X, a potent and s... Bioorg Med Chem Lett. 2007 Jan 15;17(2):385-9. | |||||
| REF 16 | Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1997 Sep;122(2):217-24. | |||||
| REF 17 | MF498 [N-{[4-(5,9-Diethoxy-6-oxo-6,8-dihydro-7H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylbenzyl]sulfonyl}-2-(2-methoxyphenyl)acetamide], a selective E prostanoid receptor 4 antagonist, relieves joint inflammation and pain in rodent models of rheumatoid and osteoarthritis. J Pharmacol Exp Ther. 2008 May;325(2):425-34. | |||||
| REF 18 | New class of biphenylene dibenzazocinones as potent ligands for the human EP1 prostanoid receptor. Bioorg Med Chem Lett. 1999 Sep 20;9(18):2699-704. | |||||
| REF 19 | The role of prostaglandin E receptor subtypes (EP1, EP2, EP3, and EP4) in bone resorption: an analysis using specific agonists for the respective EPs. Endocrinology. 2000 Apr;141(4):1554-9. | |||||
| REF 20 | Antihypertensive effects of selective prostaglandin E2 receptor subtype 1 targeting. J Clin Invest. 2007 Sep;117(9):2496-505. | |||||
| REF 21 | Characterization of the prostanoid receptor types involved in mediating calcitonin gene-related peptide release from cultured rat trigeminal neurones. Br J Pharmacol. 2001 Nov;134(6):1296-302. | |||||
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