Target Information

Target General Infomation
Target ID
T99954
Former ID
TTDS00170
Target Name
Prostacyclin receptor
Gene Name
PTGIR
Synonyms
IP prostanoid receptor; PGI receptor; Prostaglandin I2 receptor; Prostanoid IP receptor; PTGIR
Target Type
Successful
Disease Aborting second-trimester pregnancy [ICD9: 779.6; ICD10: O04]
Asthma [ICD10: J45]
Chronic renal failure [ICD9: 585.9585.1-585.5403; ICD10: N18]
Gout [ICD9: 274.00274.1274.8274.9; ICD10: M10]
Hypertension [ICD9: 401; ICD10: I10-I16]
Medical abortion [ICD9: 779.6; ICD10: O04]
Pulmonary hypertension [ICD9: 416; ICD10: I27.0, I27.2]
Pulmonary arterial hypertension [ICD9: 416; ICD10: I27.0, I27.2]
Pulmonary arterial hypertension; Thrombosis [ICD9:416, 437.6, 453, 671.5, 671.9; ICD10: I27.0, I27.2, I80-I82]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
Receptor for prostacyclin (prostaglandin I2 or PGI2).The activity of this receptor is mediated by G(s) proteins which activate adenylate cyclase.
BioChemical Class
GPCR rhodopsin
Target Validation
T99954
UniProt ID
P43119
Sequence
MADSCRNLTYVRGSVGPATSTLMFVAGVVGNGLALGILSARRPARPSAFAVLVTGLAATD
LLGTSFLSPAVFVAYARNSSLLGLARGGPALCDAFAFAMTFFGLASMLILFAMAVERCLA
LSHPYLYAQLDGPRCARLALPAIYAFCVLFCALPLLGLGQHQQYCPGSWCFLRMRWAQPG
GAAFSLAYAGLVALLVAAIFLCNGSVTLSLCRMYRQQKRHQGSLGPRPRTGEDEVDHLIL
LALMTVVMAVCSLPLTIRCFTQAVAPDSSSEMGDLLAFRFYAFNPILDPWVFILFRKAVF
QRLKLWVCCLCLGPAHGDSQTPLSQLASGRRDPRAPSAPVGKEGSCVPLSAWGEGQVEPL
PPTQQSSGSAVGTSSKAEASVACSLC
Drugs and Mode of Action
Drug(s) Dinoprost Tromethamine Drug Info Approved Aborting second-trimester pregnancy [1]
Epoprostenol Drug Info Approved Pulmonary hypertension [2], [3]
Misoprostol Drug Info Approved Medical abortion [4], [5]
Selexipag Drug Info Approved Pulmonary arterial hypertension; Thrombosis [6], [7]
Treprostinil Drug Info Approved Pulmonary arterial hypertension [2], [8]
LAROPIPRANT Drug Info Phase 4 Discovery agent [9], [10]
esuberaprost Drug Info Phase 3 Gout [11]
APD-811 Drug Info Phase 2 Pulmonary hypertension [12]
Clinprost Drug Info Discontinued in Preregistration Asthma [13]
Ataprost Drug Info Discontinued in Phase 3 Asthma [14]
YM533 Drug Info Discontinued in Phase 3 Chronic renal failure [15]
OP-2507 Drug Info Discontinued in Phase 2 Hypertension [16]
AP-227 Drug Info Terminated Discovery agent [17]
EPTALOPROST Drug Info Terminated Solid tumours [18]
Agonist AFP-07 Drug Info [19]
APD-811 Drug Info [20]
BMY 45778 Drug Info [21]
butaprost (free acid form) Drug Info [22]
carbacyclin Drug Info [22]
cicaprost Drug Info [23]
EP 157 Drug Info [24]
Epoprostenol Drug Info [25], [26], [27]
esuberaprost Drug Info [11]
isocarbacyclin Drug Info [23]
Selexipag Drug Info [28]
TEI-9063 Drug Info [21]
Treprostinil Drug Info [29]
U46619 Drug Info [22]
Inhibitor AP-227 Drug Info [30]
FR-181157 Drug Info [31]
FR-193262 Drug Info [32]
LAROPIPRANT Drug Info [33]
Modulator Ataprost Drug Info [34]
Clinprost Drug Info [35]
EPTALOPROST Drug Info [36], [37]
OP-2507 Drug Info [38]
Prostacyclin analog Drug Info [39]
YM533 Drug Info [39]
Antagonist BAY-73-1449 Drug Info [40]
Dinoprost Tromethamine Drug Info [41], [42]
Misoprostol Drug Info [41], [43], [44]
RO1138452 Drug Info [45]
RO3244794 Drug Info [45]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Neuroactive ligand-receptor interaction
Vascular smooth muscle contraction
Platelet activation
Pathway Interaction Database Thromboxane A2 receptor signaling
PathWhiz Pathway Intracellular Signalling Through Prostacyclin Receptor and Prostacyclin
Reactome Prostanoid ligand receptors
G alpha (s) signalling events
WikiPathways Prostaglandin Synthesis and Regulation
GPCRs, Class A Rhodopsin-like
Small Ligand GPCRs
Endothelin Pathways
Platelet homeostasis
GPCR ligand binding
GPCR downstream signaling
References
REF 1Drug information of Dinoprost Tromethamine, 2008. eduDrugs.
REF 2Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19.
REF 3(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: 1915).
REF 4Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
REF 5(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: 1936).
REF 6ClinicalTrials.gov (NCT01106014) Selexipag (ACT-293987) in Pulmonary Arterial Hypertension, GRIPHON Trial. U.S. National Institutes of Health.
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: 7552).
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: 5820).
REF 9ClinicalTrials.gov (NCT01126073) Niacin/Laropiprant and Endothelial Function. 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: 3356).
REF 11Specific binding of the new stable epoprostenol analogue beraprost sodium to prostacyclin receptors on human and rat platelets. Arzneimittelforschung. 1989 Apr;39(4):495-9.
REF 12ClinicalTrials.gov (NCT02279745) Long Term Safety and Efficacy of APD811 in Pulmonary Arterial Hypertension. U.S. National Institutes of Health.
REF 13Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003132)
REF 14Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002073)
REF 15Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026064)
REF 16Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005417)
REF 17Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005184)
REF 18Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003249)
REF 197,7-Difluoroprostacyclin derivative, AFP-07, a highly selective and potent agonist for the prostacyclin receptor. Prostaglandins. 1997 Feb;53(2):83-90.
REF 20Prostacyclin: An Inflammatory Paradox. Front Pharmacol. 2011; 2: 24.
REF 21Relaxant actions of nonprostanoid prostacyclin mimetics on human pulmonary artery. J Cardiovasc Pharmacol. 1997 Apr;29(4):525-35.
REF 22The 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 23Ligand 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 24Prostaglandin endoperoxide analogues which are both thromboxane receptor antagonists and prostacyclin mimetics. Br J Pharmacol. 1986 Mar;87(3):543-51.
REF 25Expression of human hexosaminidase-A phenotype depends on genes assigned to chromosomes 5 and 15. Birth Defects Orig Artic Ser. 1976;12(7):192-6.
REF 26Signaling through Gi family members in platelets. Redundancy and specificity in the regulation of adenylyl cyclase and other effectors. J Biol Chem. 2002 Nov 29;277(48):46035-42. Epub 2002 Sep 23.
REF 27Novel signaling pathways promote a paracrine wave of prostacyclin-induced vascular smooth muscle differentiation. J Mol Cell Cardiol. 2009 May;46(5):682-94. Epub 2009 Jan 23.
REF 28Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. Eur Respir J. 2012 Oct;40(4):874-80. Epub 2012 Feb 23.
REF 29Dosing considerations in the use of intravenous prostanoids in pulmonary arterial hypertension: an experience-based review. Am Heart J. 2009 Apr;157(4):625-35.
REF 30Molecular design of novel PGI2 agonists without PG skeleton, Bioorg. Med. Chem. Lett. 5(10):1071-1076 (1995).
REF 31Bioorg Med Chem Lett. 2006 Sep 15;16(18):4861-4. Epub 2006 Jul 11.Replacing the cyclohexene-linker of FR181157 leading to novel IP receptor agonists: orally active prostacyclin mimetics. Part 6.
REF 32Bioorg Med Chem Lett. 2005 Jul 1;15(13):3279-83.Discovery of new diphenyloxazole derivatives containing a pyrrolidine ring: orally active prostacyclin mimetics. Part 2.
REF 33J Med Chem. 2007 Feb 22;50(4):794-806.Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic acid (MK-0524).
REF 34Pharmacokinetics of intravenous ataprost alfadex, a new prostaglandin I2 analog in healthy volunteers. Int J Clin Pharmacol Ther Toxicol. 1993 Aug;31(8):373-5.
REF 35Protective effect of a prostaglandin I2 analog, TEI-7165, on ischemic neuronal damage in gerbils. Brain Res. 1997 Sep 26;769(2):321-8.
REF 36Bioactivation of eptaloprost in animals and man. Prostaglandins. 1993 Aug;46(2):177-89.
REF 37Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 38Effect of a prostaglandin I(2) analog on the expression of thrombomodulin in liver and spleen endothelial cells after an extensive hepatectomy. Surg Today. 2011 Feb;41(2):230-6.
REF 39(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: 345).
REF 40Vascular actions of the prostacyclin receptor antagonist BAY 73-1449 in the portal hypertensive rat. Eur J Pharmacol. 2008 Aug 20;590(1-3):322-6.
REF 41Palmitoylation of the human prostacyclin receptor. Functional implications of palmitoylation and isoprenylation. J Biol Chem. 2003 Feb 28;278(9):6947-58. Epub 2002 Dec 17.
REF 42Molecular cloning of human prostacyclin receptor cDNA and its gene expression in the cardiovascular system. Circulation. 1994 Oct;90(4):1643-7.
REF 43Structural organization and chromosomal assignment of the human prostacyclin receptor gene. Genomics. 1995 May 1;27(1):142-8.
REF 44The future potential of eicosanoids and their inhibitors in paediatric practice. Drugs. 1998 Aug;56(2):169-76.
REF 45RO1138452 and RO3244794: characterization of structurally distinct, potent and selective IP (prostacyclin) receptor antagonists. Br J Pharmacol. 2006 Feb;147(3):335-45.

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