Target Information

Target General Information

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Target ID

T76198 (Former ID: TTDS00395)

Target Name

Thromboxane A2 receptor (TBXA2R)

Synonyms

TXA2-R; TXA2 receptor; Prostanoid TP receptor

Gene Name

TBXA2R

Target Type

Successful target

[1]

Disease

[+] 4 Target-related Diseases

Diabetic foot ulcer [ICD-11: BD54]

Myocardial infarction [ICD-11: BA41-BA43]

Sexual dysfunction [ICD-11: HA00-HA01]

Coronary atherosclerosis [ICD-11: BA80]

Function

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. Receptor for thromboxane A2 (TXA2), a potent stimulator of platelet aggregation.

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BioChemical Class

GPCR rhodopsin

UniProt ID

TA2R_HUMAN

Sequence

MWPNGSSLGPCFRPTNITLEERRLIASPWFAASFCVVGLASNLLALSVLAGARQGGSHTR
SSFLTFLCGLVLTDFLGLLVTGTIVVSQHAALFEWHAVDPGCRLCRFMGVVMIFFGLSPL
LLGAAMASERYLGITRPFSRPAVASQRRAWATVGLVWAAALALGLLPLLGVGRYTVQYPG
SWCFLTLGAESGDVAFGLLFSMLGGLSVGLSFLLNTVSVATLCHVYHGQEAAQQRPRDSE
VEMMAQLLGIMVVASVCWLPLLVFIAQTVLRNPPAMSPAGQLSRTTEKELLIYLRVATWN
QILDPWVYILFRRAVLRRLQPRLSTRPRSLSLQPQLTQRSGLQ

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3D Structure

Click to Show 3D Structure of This Target

AlphaFold

ADReCS ID

BADD_A04694

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 3 Approved Drugs

Alprostadil

Drug Info

Approved

Erectile dysfunction

[2], [3]

Ridogrel

Drug Info

Approved

Acute myocardial infarction

[4]

LAROPIPRANT

Drug Info

Phase 4

Coronary heart disease

[5]

Clinical Trial Drug(s)

[+] 10 Clinical Trial Drugs

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 tumour/cancer

[16]

Discontinued Drug(s)

[+] 16 Discontinued Drugs

Domitroban

Drug Info

Discontinued in Preregistration

Thrombosis

[17], [18]

Seratrodast

Drug Info

Discontinued in Phase 3

Allergic asthma

[19]

Terutroban sodium

Drug Info

Discontinued in Phase 3

Thrombosis

[20]

ICI-192605

Drug Info

Discontinued in Phase 2

Thrombosis

[21], [22]

Linotroban

Drug Info

Discontinued in Phase 2

Thrombosis

[23]

SQ-30741

Drug Info

Discontinued in Phase 2

Thrombosis

[24]

Z-335

Drug Info

Discontinued in Phase 2

Thrombosis

[25]

CGS-22652

Drug Info

Discontinued in Phase 1

Angina pectoris

[26]

KT2-962

Drug Info

Discontinued in Phase 1

Thrombosis

[27]

KW-3635

Drug Info

Discontinued in Phase 1

Thrombosis

[28], [29]

ON-579

Drug Info

Terminated

Asthma

[30]

SQ-33961

Drug Info

Terminated

Thrombosis

[31]

Sulotroban

Drug Info

Terminated

Asthma

[32]

UP-116-77

Drug Info

Terminated

Thrombosis

[33]

Vapiprost

Drug Info

Terminated

Cardiovascular disease

[34], [35]

ZT-386

Drug Info

Terminated

Asthma

[36]

Mode of Action

[+] 5 Modes of Action

Modulator

[+] 14 Modulator drugs

Alprostadil

Drug Info

[37]

FK-070

Drug Info

[8]

KP-496

Drug Info

[10]

TAK-128

Drug Info

[11]

G-619

Drug Info

[14]

YM-57158

Drug Info

[15]

CGS-22652

Drug Info

[52]

ON-579

Drug Info

[56]

SQ-33961

Drug Info

[57]

Sulotroban

Drug Info

[58]

UP-116-77

Drug Info

[59]

Vapiprost

Drug Info

[60]

ZT-386

Drug Info

[61]

S 18204

Drug Info

[71]

Binder

[+] 1 Binder drugs

Ridogrel

Drug Info

[1]

Inhibitor

[+] 6 Inhibitor drugs

LAROPIPRANT

Drug Info

[38]

DALTROBAN

Drug Info

[44]

L-657925

Drug Info

[55]

BM-573

Drug Info

[64]

SQ-29548

Drug Info

[41], [55]

U-44069

Drug Info

[73]

Antagonist

[+] 20 Antagonist drugs

Ramatroban

Drug Info

[39]

Ifetroban sodium

Drug Info

[40]

BIBV 308

Drug Info

[40]

DT-TX-30

Drug Info

[13]

Domitroban

Drug Info

[42], [43]

Seratrodast

Drug Info

[45]

Terutroban sodium

Drug Info

[46]

ICI-192605

Drug Info

[47]

Linotroban

Drug Info

[48]

SQ-30741

Drug Info

[49], [50]

Z-335

Drug Info

[50], [51]

KT2-962

Drug Info

[50], [53]

KW-3635

Drug Info

[54]

AH23848

Drug Info

[41]

I-SAP

Drug Info

[68]

ONO-3708

Drug Info

[69]

ONO-8809

Drug Info

[50], [70]

[125I]PTA-OH

Drug Info

[75]

[125I]SAP

Drug Info

[68]

[125I]SQ-29548

Drug Info

[76]

Agonist

[+] 17 Agonist drugs

PGF2alpha

Drug Info

[41]

10,10-difluoro TXA2

Drug Info

[62]

AGN 191976

Drug Info

[63]

AGN192093

Drug Info

[63]

butaprost (free acid form)

Drug Info

[41]

carbacyclin

Drug Info

[41]

carbocyclic thromboxane A2

Drug Info

[65]

cloprostenol

Drug Info

[41]

EP 171

Drug Info

[66]

fluprostenol

Drug Info

[41]

I-BOP

Drug Info

[67]

M&B 28767

Drug Info

[41]

PGH2

Drug Info

[65]

SQ 26655

Drug Info

[72]

STA2

Drug Info

[67]

U46619

Drug Info

[41]

[125I]BOP

Drug Info

[74]

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"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

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Regulators

Top

Target-regulating microRNAs

Target-regulating microRNAs Info

Target-regulating Transcription Factors

Target-regulating Transcription Factors Info

Target-interacting Proteins

Target-interacting Proteins Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

Top

KEGG Pathway

[+] 3 KEGG Pathways

Calcium signaling pathway

Neuroactive ligand-receptor interaction

Platelet activation

Reactome

[+] 4 Reactome Pathways

Prostanoid ligand receptors

G alpha (q) signalling events

G alpha (12/13) signalling events

Thromboxane signalling through TP receptor

WikiPathways

[+] 6 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

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

Top

REF 1

Chronic ouabain treatment exacerbates blood pressure elevation in spontaneously hypertensive rats: the role of vascular mechanisms. J Hypertens. 2009 Jun;27(6):1233-42.

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: 1882).

REF 3

Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome. Expert Opin Emerg Drugs. 2007 Sep;12(3):461-77.

REF 4

Inhibition of cytochromes p450: existing and new promising therapeutic targets. Drug Metab Rev. 2007;39(2-3):481-99.

REF 5

ClinicalTrials.gov (NCT01126073) A Double Blind, Randomized Study to Compare Influence of Niacin/Laropiprant on Functional and Morphological Characteristics of Arterial Wall and Parameters of Inflammation in Subjects With Coronary Heart Disease Already Treated With a Statin in Miran Sebestjen, University Medical Centre Ljubljana.

REF 6

REF 7

ClinicalTrials.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 8

Pharmacokinetic 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

REF 10

Effects 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 11

ClinicalTrials.gov (NCT00229437) Efficacy and Safety Study of TAK-128 in Treating Subjects With Diabetic Peripheral Neuropathy. U.S. National Institutes of Health.

REF 12

ClinicalTrials.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 13

DTTX30, 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 14

G 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 15

In 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 16

Stereocontrolled organocatalytic synthesis of prostaglandin PGF2alpha in seven steps. Nature. 2012 Sep 13;489(7415):278-81.

REF 17

REF 18

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001843)

REF 19

Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.

REF 20

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011626)

REF 21

REF 22

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000402)

REF 23

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003261)

REF 24

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000361)

REF 25

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006051)

REF 26

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001983)

REF 27

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002792)

REF 28

REF 29

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000338)

REF 30

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003601)

REF 31

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001755)

REF 32

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000039)

REF 33

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005083)

REF 34

REF 35

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000070)

REF 36

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004057)

REF 37

Flow 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 38

Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydroc... J Med Chem. 2007 Feb 22;50(4):794-806.

REF 39

Participation in cysteinyl leukotrienes and thromboxane A2 in nasal congestion model in Brown Norway rats. Int Immunopharmacol. 2007 Nov;7(11):1483-7.

REF 40

AT-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 41

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 42

The 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 43

Mouse thromboxane A2 receptor: cDNA cloning, expression and northern blot analysis. Biochem Biophys Res Commun. 1992 May 15;184(3):1197-203.

REF 44

Synthesis and thromboxane A2/prostaglandin H2 receptor antagonistic activity of phenol derivatives. J Med Chem. 1992 Jun 12;35(12):2202-9.

REF 45

Thromboxane A2 inhibition: therapeutic potential in bronchial asthma. Am J Respir Med. 2002;1(1):11-7.

REF 46

Terutroban and endothelial TP receptors in atherogenesis. Med Sci (Paris). 2006 Apr;22(4):437-43.

REF 47

The 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 48

Effects 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 49

Influence 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 50

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 51

Pharmacokinetic 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 52

Blood pressure effects of thromboxane A2 blockade in spontaneously hypertensive rats. Clin Exp Pharmacol Physiol. 1993 Nov;20(11):679-87.

REF 53

Azulene 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 54

Antithrombotic effects of KW-3635, a thromboxane A2-receptor antagonist, in guinea pigs. Jpn J Pharmacol. 1994 Jun;65(2):93-8.

REF 55

Novel synthesis and biochemical properties of an [125I]-labeled photoaffinity probe for thromboxane A2/prostaglandin H2 receptors. J Med Chem. 1991 Apr;34(4):1511-4.

REF 56

The effect of a TXA2 receptor antagonist ON-579 on experimental allergic reactions. Prostaglandins Leukot Essent Fatty Acids. 1995 Aug;53(2):123-33.

REF 57

Conformationally-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 58

The PGI2-analogue iloprost and the TXA2-receptor antagonist sulotroban synergistically inhibit TXA2-dependent platelet activation. Prostaglandins. 1988 Dec;36(6):751-60.

REF 59

Synthesis 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 60

Effects 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 61

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004057)

REF 62

Difluorothromboxane 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 63

Evidence 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 64

Synthesis and pharmacological evaluation of novel nitrobenzenic thromboxane modulators as antiplatelet agents acting on both the alpha and beta iso... J Med Chem. 2006 Jun 15;49(12):3701-9.

REF 65

Effects 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 66

EP 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 67

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 68

7-[(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 69

Characterization 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 70

Anti-thrombotic effect of ONO-8809, a novel TXA2/PG endoperoxide receptor antagonist. Adv Prostaglandin Thromboxane Leukot Res. 1991;21B:599-602.

REF 71

Antithrombotic effects of S 18886, a novel orally active thromboxane A2 receptor antagonist. J Thromb Haemost. 2004 Mar;2(3):492-8.

REF 72

Synthesis 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 73

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 74

Characterization of an 125I-labeled thromboxane A2/prostaglandin H2 receptor agonist. J Pharmacol Exp Ther. 1989 Nov;251(2):557-62.

REF 75

Binding of thromboxane A2/prostaglandin H2 agonists to human platelets. Br J Pharmacol. 1987 May;91(1):223-7.

REF 76

Characterization 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.

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