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 Allergic asthma [ICD9: 493, 995.3; ICD10: J45, T78.4]
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]
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 [1], [2]
Ridogrel Drug Info Approved Acute myocardial infarction [3]
LAROPIPRANT Drug Info Phase 4 Discovery agent [4], [5]
Ramatroban Drug Info Phase 2/3 Perennial allergic rhinitis [6], [7]
FK-070 Drug Info Phase 2 Angina pectoris [8]
Ifetroban sodium Drug Info Phase 2 Thrombosis [9]
KP-496 Drug Info Phase 2 Asthma [10]
TAK-128 Drug Info Phase 2 Diabetic neuropathy [11]
BIBV 308 Drug Info Phase 1 Peripheral vascular disease [12]
DT-TX-30 Drug Info Phase 1 Angina pectoris [13]
G-619 Drug Info Phase 1 Thrombosis [14]
YM-57158 Drug Info Phase 1 Allergic rhinitis [15]
PGF2alpha Drug Info Clinical trial Solid tumours [16]
Domitroban Drug Info Discontinued in Preregistration Thrombosis [17], [18]
DALTROBAN Drug Info Discontinued in Phase 3 Discovery agent [19], [20]
Seratrodast Drug Info Discontinued in Phase 3 Allergic asthma [21]
Terutroban sodium Drug Info Discontinued in Phase 3 Thromboembolism [22]
ICI-192605 Drug Info Discontinued in Phase 2 Thrombosis [23], [24]
Linotroban Drug Info Discontinued in Phase 2 Thrombosis [25]
SQ-30741 Drug Info Discontinued in Phase 2 Thrombosis [26]
Z-335 Drug Info Discontinued in Phase 2 Thrombosis [27]
CGS-22652 Drug Info Discontinued in Phase 1 Angina pectoris [28]
KT2-962 Drug Info Discontinued in Phase 1 Thrombosis [29]
KW-3635 Drug Info Discontinued in Phase 1 Thrombosis [30], [31]
L-657925 Drug Info Terminated Discovery agent [32]
ON-579 Drug Info Terminated Asthma [33]
SQ-29548 Drug Info Terminated Discovery agent [34], [35]
SQ-33961 Drug Info Terminated Thromboembolism [36]
Sulotroban Drug Info Terminated Asthma [37]
UP-116-77 Drug Info Terminated Thromboembolism [38]
Vapiprost Drug Info Terminated Cardiovascular disorder [39], [40]
ZT-386 Drug Info Terminated Asthma [41]
Agonist 10,10-difluoro TXA2 Drug Info [42]
AGN 191976 Drug Info [43]
AGN192093 Drug Info [43]
butaprost (free acid form) Drug Info [44]
carbacyclin Drug Info [44]
carbocyclic thromboxane A2 Drug Info [45]
cloprostenol Drug Info [44]
EP 171 Drug Info [46]
fluprostenol Drug Info [44]
I-BOP Drug Info [47]
M&B 28767 Drug Info [44]
PGF2alpha Drug Info [44]
SQ 26655 Drug Info [48]
STA2 Drug Info [47]
U46609 Drug Info [45]
U46619 Drug Info [44]
[125I]BOP Drug Info [49]
[3H]U46619 Drug Info [44]
Antagonist AH23848 Drug Info [44]
BIBV 308 Drug Info [50]
Domitroban Drug Info [51]
DT-TX-30 Drug Info [13]
I-SAP Drug Info [52]
ICI-192605 Drug Info [53]
Ifetroban sodium Drug Info [50]
KT2-962 Drug Info [54], [55]
KW-3635 Drug Info [56]
Linotroban Drug Info [57]
ONO-3708 Drug Info [58]
ONO-8809 Drug Info [59], [55]
Ramatroban Drug Info [60]
Seratrodast Drug Info [61]
SQ-30741 Drug Info [62], [55]
Terutroban sodium Drug Info [63]
Z-335 Drug Info [64], [55]
[125I]PTA-OH Drug Info [65]
[125I]SAP Drug Info [52]
[125I]SQ-29548 Drug Info [66]
[3H]S-145 Drug Info [67]
[3H]SQ-29548 Drug Info [44]
Modulator Alprostadil Drug Info [68]
CGS-22652 Drug Info
FK-070 Drug Info [8]
G-619 Drug Info [14]
KP-496 Drug Info [10]
ON-579 Drug Info [69]
S 18204 Drug Info
SQ-33961 Drug Info [70]
Sulotroban Drug Info [71]
TAK-128 Drug Info [11]
UP-116-77 Drug Info [72]
Vapiprost Drug Info [73]
YM-57158 Drug Info [15]
ZT-386 Drug Info [74]
Inhibitor BM-573 Drug Info [75]
DALTROBAN Drug Info [76]
L-657925 Drug Info [77]
LAROPIPRANT Drug Info [78]
SQ-29548 Drug Info [77]
U-44069 Drug Info [79]
Binder Ridogrel Drug Info [80]
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
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REF 3Inhibition of cytochromes p450: existing and new promising therapeutic targets. Drug Metab Rev. 2007;39(2-3):481-99.
REF 4ClinicalTrials.gov (NCT01126073) Niacin/Laropiprant and Endothelial Function. U.S. National Institutes of Health.
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: 3356).
REF 6ClinicalTrials.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 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: 1911).
REF 8Pharmacokinetic 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 9(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 10Effects 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.
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REF 14G 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.
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REF 18Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001843)
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REF 27Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006051)
REF 28Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001983)
REF 29Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002792)
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REF 31Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000338)
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REF 33Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003601)
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REF 35Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001848)
REF 36Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001755)
REF 37Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000039)
REF 38Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005083)
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. (Ligand id: 1976).
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REF 50AT-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.
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REF 527-[(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 53The 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.
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REF 55Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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REF 59Anti-thrombotic effect of ONO-8809, a novel TXA2/PG endoperoxide receptor antagonist. Adv Prostaglandin Thromboxane Leukot Res. 1991;21B:599-602.
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REF 62Influence 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 63Terutroban and endothelial TP receptors in atherogenesis. Med Sci (Paris). 2006 Apr;22(4):437-43.
REF 64Pharmacokinetic 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.
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REF 66Characterization 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 67Mouse thromboxane A2 receptor: cDNA cloning, expression and northern blot analysis. Biochem Biophys Res Commun. 1992 May 15;184(3):1197-203.
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REF 71The PGI2-analogue iloprost and the TXA2-receptor antagonist sulotroban synergistically inhibit TXA2-dependent platelet activation. Prostaglandins. 1988 Dec;36(6):751-60.
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REF 78J 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 79J 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.
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