Target Information

Target General Infomation
Target ID
T76198
Former ID
TTDS00395
Target Name
Thromboxane A2 receptor
Gene Name
TBXA2R
Synonyms
Prostanoid TP receptor; TXA2 receptor; TXA2-R; TBXA2R
Target Type
Successful
Disease Angina pectoris [ICD9: 413; ICD10: I20]
Allergic rhinitis [ICD9: 472.0, 477, 995.3; ICD10: J00, J30, J31.0, T78.4]
Acute myocardial infarction [ICD9: 410; ICD10: I21-I22]
Asthma [ICD10: J45]
Allergic asthma [ICD9: 493, 995.3; ICD10: J45, T78.4]
Cardiovascular disorder [ICD10: I00-I99]
Diabetic neuropathy [ICD9: 250, 250.6, 356.0, 356.8; ICD10: E11.40]
Erectile dysfunction [ICD9: 302.72, 607.84; ICD10: F52.2, N48.4]
Peripheral vascular disease [ICD9: 443.9; ICD10: I73.9]
Perennial allergic rhinitis [ICD9: 204.0, 472.0, 477, 995.3; ICD10: C91.0, J00, J30, J31.0, T78.4]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Thromboembolism [ICD9: 437.6, 453, 671.5, 671.9; ICD10: I80-I82]
Thrombosis [ICD9: 437.6, 453, 671.5, 671.9; ICD10: I80-I82]
Unspecified [ICD code not available]
Function
Receptor for thromboxane A2 (TXA2), a potentstimulator of platelet aggregation. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system. In the kidney, the binding of TXA2 to glomerular TP receptors causes intense vasoconstriction. Activates phospholipase C. Isoform 1 activates adenylyl cyclase. Isoform 2 inhibits adenylyl cyclase.
BioChemical Class
GPCR rhodopsin
Target Validation
T76198
UniProt ID
P21731
Sequence
MWPNGSSLGPCFRPTNITLEERRLIASPWFAASFCVVGLASNLLALSVLAGARQGGSHTR
SSFLTFLCGLVLTDFLGLLVTGTIVVSQHAALFEWHAVDPGCRLCRFMGVVMIFFGLSPL
LLGAAMASERYLGITRPFSRPAVASQRRAWATVGLVWAAALALGLLPLLGVGRYTVQYPG
SWCFLTLGAESGDVAFGLLFSMLGGLSVGLSFLLNTVSVATLCHVYHGQEAAQQRPRDSE
VEMMAQLLGIMVVASVCWLPLLVFIAQTVLRNPPAMSPAGQLSRTTEKELLIYLRVATWN
QILDPWVYILFRRAVLRRLQPRLSTRPRSLSLQPQLTQRSGLQ
Drugs and Mode of Action
Drug(s) Alprostadil Drug Info Approved Erectile dysfunction [536500], [539183]
Ridogrel Drug Info Approved Acute myocardial infarction [536491]
LAROPIPRANT Drug Info Phase 4 Discovery agent [523049], [540312]
Ramatroban Drug Info Phase 2/3 Perennial allergic rhinitis [521819], [539212]
FK-070 Drug Info Phase 2 Angina pectoris [534202]
Ifetroban sodium Drug Info Phase 2 Thrombosis [539284]
KP-496 Drug Info Phase 2 Asthma [528550]
TAK-128 Drug Info Phase 2 Diabetic neuropathy [521733]
BIBV 308 Drug Info Phase 1 Peripheral vascular disease [524888]
DT-TX-30 Drug Info Phase 1 Angina pectoris [534431]
G-619 Drug Info Phase 1 Thrombosis [534091]
YM-57158 Drug Info Phase 1 Allergic rhinitis [534743]
PGF2alpha Drug Info Clinical trial Solid tumours [532003]
Domitroban Drug Info Discontinued in Preregistration Thrombosis [539275], [545002]
DALTROBAN Drug Info Discontinued in Phase 3 Discovery agent [539283], [544557]
Seratrodast Drug Info Discontinued in Phase 3 Allergic asthma [536361]
Terutroban sodium Drug Info Discontinued in Phase 3 Thromboembolism [546968]
ICI-192605 Drug Info Discontinued in Phase 2 Thrombosis [541321], [544641]
Linotroban Drug Info Discontinued in Phase 2 Thrombosis [545440]
SQ-30741 Drug Info Discontinued in Phase 2 Thrombosis [544628]
Z-335 Drug Info Discontinued in Phase 2 Thrombosis [546050]
CGS-22652 Drug Info Discontinued in Phase 1 Angina pectoris [545054]
KT2-962 Drug Info Discontinued in Phase 1 Thrombosis [545314]
KW-3635 Drug Info Discontinued in Phase 1 Thrombosis [539273], [544622]
L-657925 Drug Info Terminated Discovery agent [544623]
ON-579 Drug Info Terminated Asthma [545526]
SQ-29548 Drug Info Terminated Discovery agent [539277], [545003]
SQ-33961 Drug Info Terminated Thromboembolism [544974]
Sulotroban Drug Info Terminated Asthma [544519]
UP-116-77 Drug Info Terminated Thromboembolism [545861]
Vapiprost Drug Info Terminated Cardiovascular disorder [539272], [544530]
ZT-386 Drug Info Terminated Asthma [545658]
Agonist 10,10-difluoro TXA2 Drug Info [533342]
AGN 191976 Drug Info [534256]
AGN192093 Drug Info [534256]
butaprost (free acid form) Drug Info [525673]
carbacyclin Drug Info [525673]
carbocyclic thromboxane A2 Drug Info [526825]
cloprostenol Drug Info [525673]
EP 171 Drug Info [533341]
fluprostenol Drug Info [525673]
I-BOP Drug Info [534478]
M&B 28767 Drug Info [525673]
PGF2alpha Drug Info [525673]
SQ 26655 Drug Info [533502]
STA2 Drug Info [534478]
U46609 Drug Info [526825]
U46619 Drug Info [525673]
[125I]BOP Drug Info [532986]
[3H]U46619 Drug Info [525673]
Antagonist AH23848 Drug Info [525673]
BIBV 308 Drug Info [536029]
Domitroban Drug Info [533694]
DT-TX-30 Drug Info [534431]
I-SAP Drug Info [526809]
ICI-192605 Drug Info [529402]
Ifetroban sodium Drug Info [536029]
KT2-962 Drug Info [534176], [551871]
KW-3635 Drug Info [533825]
Linotroban Drug Info [534495]
ONO-3708 Drug Info [533405]
ONO-8809 Drug Info [529292], [551871]
Ramatroban Drug Info [536488]
Seratrodast Drug Info [535888]
SQ-30741 Drug Info [529394], [551871]
Terutroban sodium Drug Info [528120]
Z-335 Drug Info [526369], [551871]
[125I]PTA-OH Drug Info [533468]
[125I]SAP Drug Info [526809]
[125I]SQ-29548 Drug Info [533391]
[3H]S-145 Drug Info [526796]
[3H]SQ-29548 Drug Info [525673]
Modulator Alprostadil Drug Info [534906]
CGS-22652 Drug Info
FK-070 Drug Info [534202]
G-619 Drug Info [534091]
KP-496 Drug Info [528550]
ON-579 Drug Info [533593]
S 18204 Drug Info
SQ-33961 Drug Info [551648]
Sulotroban Drug Info [532727]
TAK-128 Drug Info [521733]
UP-116-77 Drug Info [534051]
Vapiprost Drug Info [544028]
YM-57158 Drug Info [534743]
ZT-386 Drug Info [545659]
Inhibitor BM-573 Drug Info [528239]
DALTROBAN Drug Info [527205]
L-657925 Drug Info [529310]
LAROPIPRANT Drug Info [528672]
SQ-29548 Drug Info [529310]
U-44069 Drug Info [529789]
Binder Ridogrel Drug Info [537194]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Calcium signaling pathway
Neuroactive ligand-receptor interaction
Platelet activation
Reactome Prostanoid ligand receptors
G alpha (q) signalling events
G alpha (12/13) signalling events
Thromboxane signalling through TP receptor
WikiPathways GPCRs, Class A Rhodopsin-like
Gastrin-CREB signalling pathway via PKC and MAPK
Small Ligand GPCRs
Signal amplification
GPCR ligand binding
GPCR downstream signaling
References
Ref 521733ClinicalTrials.gov (NCT00229437) Efficacy and Safety Study of TAK-128 in Treating Subjects With Diabetic Peripheral Neuropathy. U.S. National Institutes of Health.
Ref 521819ClinicalTrials.gov (NCT00311051) Ramatroban/Montelukast Versus Montelukast/Placebo on the Early Allergic Reaction in Asthma Sensitive to House Dust Mite. U.S. National Institutes of Health.
Ref 523049ClinicalTrials.gov (NCT01126073) Niacin/Laropiprant and Endothelial Function. U.S. National Institutes of Health.
Ref 524888ClinicalTrials.gov (NCT02223013) Relative Bioavailability and Tolerability of Two New Different Extended Release Capsules of BIBV 308 SE, Versus a Solution of BIBV 308 SE in Healthy Subjects. U.S. National Institutes of Health.
Ref 528550Effects of KP-496, a novel dual antagonist for leukotriene D4 and thromboxane A2 receptors, on contractions induced by various agonists in the guinea pig trachea. Allergol Int. 2006 Dec;55(4):403-10.
Ref 532003Stereocontrolled organocatalytic synthesis of prostaglandin PGF2alpha in seven steps. Nature. 2012 Sep 13;489(7415):278-81.
Ref 534091G 619, a dual thromboxane synthase inhibitor and thromboxane A2 receptor antagonist, inhibits tumor necrosis factor-alpha biosynthesis. Eur J Pharmacol. 1995 Nov 3;286(1):31-9.
Ref 534202Pharmacokinetic and pharmacodynamic properties of FK070 (KDI-792), a novel thromboxane receptor antagonist/thromboxane synthetase inhibitor, after single and multiple oral administrations to healthy volunteers. J Pharm Pharmacol. 1996 Apr;48(4):380-5.
Ref 534431DTTX30, a combined thromboxane receptor antagonist and thromboxane synthetase inhibitor, prevents coronary thrombosis in anesthetized dogs. Basic Res Cardiol. 1997 Jun;92(3):181-90.
Ref 534743In vitro pharmacologic profile of YM158, a new dual antagonist for LTD4 and TXA2 receptors. J Pharmacol Exp Ther. 1998 Nov;287(2):633-9.
Ref 536361Natural 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 536491Inhibition of cytochromes p450: existing and new promising therapeutic targets. Drug Metab Rev. 2007;39(2-3):481-99.
Ref 536500Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome. Expert Opin Emerg Drugs. 2007 Sep;12(3):461-77.
Ref 539183(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: 1882).
Ref 539212(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: 1911).
Ref 539272(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: 1976).
Ref 539273(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: 1977).
Ref 539275(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: 1979).
Ref 539277(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: 1980).
Ref 539283(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: 1986).
Ref 539284(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: 1987).
Ref 540312(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 541321(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: 6072).
Ref 544519Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000039)
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Ref 546968Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011626)
Ref 521733ClinicalTrials.gov (NCT00229437) Efficacy and Safety Study of TAK-128 in Treating Subjects With Diabetic Peripheral Neuropathy. U.S. National Institutes of Health.
Ref 525673The 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 526369Pharmacokinetic and pharmacodynamic properties of a new thromboxane receptor antagonist (Z-335) after single and multiple oral administrations to healthy volunteers. J Clin Pharmacol. 2002 Jul;42(7):782-90.
Ref 526796Mouse thromboxane A2 receptor: cDNA cloning, expression and northern blot analysis. Biochem Biophys Res Commun. 1992 May 15;184(3):1197-203.
Ref 5268097-[(1R,2S,3S,5R)-6,6-dimethyl-3-(4- iodobenzenesulfonylamino)bicyclo[3.1.1]hept-2-yl]-5(Z)-heptenoic acid: a novel high-affinity radiolabeled antagonist for platelet thromboxane A2/prostaglandin H2 receptors. J Pharmacol Exp Ther. 1992 Aug;262(2):632-7.
Ref 526825Effects of KW-3635, a novel dibenzoxepin derivative of a selective thromboxane A2 antagonist, on human, guinea pig and rat platelets. Jpn J Pharmacol. 1992 Jul;59(3):357-64.
Ref 527205J Med Chem. 1992 Jun 12;35(12):2202-9.Synthesis and thromboxane A2/prostaglandin H2 receptor antagonistic activity of phenol derivatives.
Ref 528120Terutroban and endothelial TP receptors in atherogenesis. Med Sci (Paris). 2006 Apr;22(4):437-43.
Ref 528239J Med Chem. 2006 Jun 15;49(12):3701-9.Synthesis and pharmacological evaluation of novel nitrobenzenic thromboxane modulators as antiplatelet agents acting on both the alpha and beta isoforms of the human thromboxane receptor.
Ref 528550Effects of KP-496, a novel dual antagonist for leukotriene D4 and thromboxane A2 receptors, on contractions induced by various agonists in the guinea pig trachea. Allergol Int. 2006 Dec;55(4):403-10.
Ref 528672J 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 529292Anti-thrombotic effect of ONO-8809, a novel TXA2/PG endoperoxide receptor antagonist. Adv Prostaglandin Thromboxane Leukot Res. 1991;21B:599-602.
Ref 529310J Med Chem. 1991 Apr;34(4):1511-4.Novel synthesis and biochemical properties of an [125I]-labeled photoaffinity probe for thromboxane A2/prostaglandin H2 receptors.
Ref 529394Influence of SQ 30741 on thromboxane receptor-mediated responses in the feline pulmonary vascular bed. J Appl Physiol (1985). 1991 Nov;71(5):2012-8.
Ref 529402The effects of thromboxane receptor blockade on platelet aggregation and digital skin blood flow in patients with secondary Raynaud's syndrome. Rheumatol Int. 1991;11(4-5):163-8.
Ref 529789J 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 532727The PGI2-analogue iloprost and the TXA2-receptor antagonist sulotroban synergistically inhibit TXA2-dependent platelet activation. Prostaglandins. 1988 Dec;36(6):751-60.
Ref 532986Characterization of an 125I-labeled thromboxane A2/prostaglandin H2 receptor agonist. J Pharmacol Exp Ther. 1989 Nov;251(2):557-62.
Ref 533341EP 171: a high affinity thromboxane A2-mimetic, the actions of which are slowly reversed by receptor blockade. Br J Pharmacol. 1989 Apr;96(4):875-87.
Ref 533342Difluorothromboxane A2 and stereoisomers: stable derivatives of thromboxane A2 with differential effects on platelets and blood vessels. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5600-4.
Ref 533391Characterization of [5,6-3H]SQ 29,548 as a high affinity radioligand, binding to thromboxane A2/prostaglandin H2-receptors in human platelets. J Pharmacol Exp Ther. 1988 Jun;245(3):786-92.
Ref 533405Characterization of U46619 binding in unactivated, intact human platelets and determination of binding site affinities of four TXA2/PGH2 receptor antagonists (13-APA, BM 13.177, ONO 3708 and SQ 29,548). Thromb Res. 1986 Feb 15;41(4):471-81.
Ref 533468Binding of thromboxane A2/prostaglandin H2 agonists to human platelets. Br J Pharmacol. 1987 May;91(1):223-7.
Ref 533502Synthesis and in vitro pharmacology of 7-oxabicyclo[2.2.1]heptane analogues of thromboxane A2/PGH2. J Med Chem. 1985 Nov;28(11):1580-90.
Ref 533593The effect of a TXA2 receptor antagonist ON-579 on experimental allergic reactions. Prostaglandins Leukot Essent Fatty Acids. 1995 Aug;53(2):123-33.
Ref 533694The effect of a novel thromboxane A2 (TXA2) receptor antagonist (S-1452) on the antigen-induced bronchoconstriction and airway hyperresponsiveness in guinea pigs. Prostaglandins Leukot Essent Fatty Acids. 1993 May;48(5):343-9.
Ref 533825Antithrombotic effects of KW-3635, a thromboxane A2-receptor antagonist, in guinea pigs. Jpn J Pharmacol. 1994 Jun;65(2):93-8.
Ref 534051Synthesis and structure-activity relationships of novel benzimidazole and imidazo[4,5-b]pyridine acid derivatives as thromboxane A2 receptor antagonists. J Med Chem. 1993 Apr 30;36(9):1175-87.
Ref 534091G 619, a dual thromboxane synthase inhibitor and thromboxane A2 receptor antagonist, inhibits tumor necrosis factor-alpha biosynthesis. Eur J Pharmacol. 1995 Nov 3;286(1):31-9.
Ref 534176Azulene derivatives as TXA2/PGH2 receptor antagonists--II. Synthesis and biological activity of 6-mono- and 6-dihydroxylated-isopropylazulenes. Bioorg Med Chem. 1996 Apr;4(4):575-91.
Ref 534202Pharmacokinetic and pharmacodynamic properties of FK070 (KDI-792), a novel thromboxane receptor antagonist/thromboxane synthetase inhibitor, after single and multiple oral administrations to healthy volunteers. J Pharm Pharmacol. 1996 Apr;48(4):380-5.
Ref 534256Evidence for human thromboxane receptor heterogeneity using a novel series of 9,11-cyclic carbonate derivatives of prostaglandin F2 alpha. Br J Pharmacol. 1996 Mar;117(6):1171-80.
Ref 534431DTTX30, a combined thromboxane receptor antagonist and thromboxane synthetase inhibitor, prevents coronary thrombosis in anesthetized dogs. Basic Res Cardiol. 1997 Jun;92(3):181-90.
Ref 534478Ligand 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 534495Effects of the novel thromboxane (TXA2) receptor antagonist linotroban on inulin and para-aminohippuric acid clearances in the conscious male and female rat. Arzneimittelforschung. 1997 Sep;47(9):1026-30.
Ref 534743In vitro pharmacologic profile of YM158, a new dual antagonist for LTD4 and TXA2 receptors. J Pharmacol Exp Ther. 1998 Nov;287(2):633-9.
Ref 534906Flow after prostaglandin E1 is mediated by receptor-coupled adenylyl cyclase in human anterior segments. Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2622-6.
Ref 535888Thromboxane A2 inhibition: therapeutic potential in bronchial asthma. Am J Respir Med. 2002;1(1):11-7.
Ref 536029AT-1 receptor antagonism modifies the mediation of endothelin-1, thromboxane A2, and catecholamines in the renal constrictor response to angiotensin II. Kidney Int Suppl. 2005 Jan;(93):S3-9.
Ref 536488Participation in cysteinyl leukotrienes and thromboxane A2 in nasal congestion model in Brown Norway rats. Int Immunopharmacol. 2007 Nov;7(11):1483-7. Epub 2007 Jun 26.
Ref 537194Chronic ouabain treatment exacerbates blood pressure elevation in spontaneously hypertensive rats: the role of vascular mechanisms. J Hypertens. 2009 Jun;27(6):1233-42.
Ref 544028Effects of vapiprost, a novel thromboxane receptor antagonist, on thrombus formation and vascular patency after thrombolysis by tissue-type plasminogen activator.. Br J Pharmacol. 1992 July; 106(3): 533-538.
Ref 545659Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004057)
Ref 551648Conformationally-restricted analogs of TXA2 antagonist SQ 33,961: Receptor binding conformation of the carboxyl sidechain. Bioorganic & Medicinal Chemistry Letters Volume 1, Issue 9, 1991, Pages 465-470.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

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