Target Information

Target General Infomation
Target ID
T78356
Former ID
TTDC00086
Target Name
Thromboxane-A synthase
Gene Name
TBXAS1
Synonyms
TS; TXA synthase; TXS; Thromboxane A2 synthase; TBXAS1
Target Type
Clinical Trial
Disease Angina pectoris [ICD9: 413; ICD10: I20]
Asthma [ICD10: J45]
Cardiac arrhythmias [ICD9: 427; ICD10: I47-I49]
Inflammatory bowel disease [ICD9: 555, 556; ICD10: K50, K51]
Nephritis [ICD10: N00-N19, N25-N29]
Thromboembolism [ICD9: 437.6, 453, 671.5, 671.9; ICD10: I80-I82]
Type 2 diabetes [ICD9: 250; ICD10: E11]
Thrombosis [ICD9: 437.6, 453, 671.5, 671.9; ICD10: I80-I82]
Unspecified [ICD code not available]
BioChemical Class
Intramolecular oxidoreductases
Target Validation
T78356
UniProt ID
P24557
EC Number
EC 5.3.99.5
Sequence
MEALGFLKLEVNGPMVTVALSVALLALLKWYSTSAFSRLEKLGLRHPKPSPFIGNLTFFR
QGFWESQMELRKLYGPLCGYYLGRRMFIVISEPDMIKQVLVENFSNFTNRMASGLEFKSV
ADSVLFLRDKRWEEVRGALMSAFSPEKLNEMVPLISQACDLLLAHLKRYAESGDAFDIQR
CYCNYTTDVVASVAFGTPVDSWQAPEDPFVKHCKRFFEFCIPRPILVLLLSFPSIMVPLA
RILPNKNRDELNGFFNKLIRNVIALRDQQAAEERRRDFLQMVLDARHSASPMGVQDFDIV
RDVFSSTGCKPNPSRQHQPSPMARPLTVDEIVGQAFIFLIAGYEIITNTLSFATYLLATN
PDCQEKLLREVDVFKEKHMAPEFCSLEEGLPYLDMVIAETLRMYPPAFRFTREAAQDCEV
LGQRIPAGAVLEMAVGALHHDPEHWPSPETFNPERFTAEARQQHRPFTYLPFGAGPRSCL
GVRLGLLEVKLTLLHVLHKFRFQACPETQVPLQLESKSALGPKNGVYIKIVSR
Drugs and Mode of Action
Drug(s) PYRIDINE Drug Info Phase 4 Discovery agent [1]
NM-702 Drug Info Phase 3 Angina pectoris [2]
E-6700 Drug Info Phase 2 Asthma [3]
EV-077 Drug Info Phase 2 Type 2 diabetes [4]
FK-070 Drug Info Phase 2 Angina pectoris [5]
G-619 Drug Info Phase 1 Thrombosis [6]
NV-52 Drug Info Phase 1 Inflammatory bowel disease [7]
ONO-1301 Drug Info Preclinical Angina pectoris [8], [9]
Satigrel Drug Info Discontinued in Preregistration Thromboembolism [10]
Imitrodast Drug Info Discontinued in Phase 2 Asthma [11]
MILACAINIDE TARTRATE Drug Info Discontinued in Phase 2 Cardiac arrhythmias [12]
Rolafagrel Drug Info Discontinued in Phase 2 Nephritis [13]
CGS-13080 Drug Info Terminated Asthma [14]
Dazoxiben Drug Info Terminated Discovery agent [15], [16]
Inhibitor 2-(10-Imidazol-1-yl-decyl)-isoindole-1,3-dione Drug Info [17]
2-(6-Imidazol-1-yl-hexyl)-isoindole-1,3-dione Drug Info [17]
2-(8-Imidazol-1-yl-octyl)-isoindole-1,3-dione Drug Info [17]
4-Methyl-pyridine Drug Info [18]
5-(2-Imidazol-1-yl-ethyl)-7,8-dihydro-quinoline Drug Info [19]
5-Imidazol-1-yl-5,6,7,8-tetrahydro-quinoline Drug Info [19]
6-Imidazol-1-yl-isoquinoline Drug Info [19]
CGS-13080 Drug Info [20]
Dazoxiben Drug Info [21]
Imitrodast Drug Info [22]
NM-702 Drug Info [23]
NV-52 Drug Info [24], [25]
ONO-1581 Drug Info [26]
PYRIDINE Drug Info [18]
Rolafagrel Drug Info [27]
Modulator CV-6504.HCL Drug Info [28]
E-6700 Drug Info [3]
EV-077 Drug Info
FK-070 Drug Info [5]
G-619 Drug Info [6]
Satigrel Drug Info [29]
Antagonist MILACAINIDE TARTRATE Drug Info [30]
Agonist ONO-1301 Drug Info [31]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
BioCyc Pathway C20 prostanoid biosynthesis
KEGG Pathway Arachidonic acid metabolism
Metabolic pathways
Platelet activation
PathWhiz Pathway Arachidonic Acid Metabolism
WikiPathways Prostaglandin Synthesis and Regulation
Arachidonic acid metabolism
Phase 1 - Functionalization of compounds
Eicosanoid Synthesis
References
REF 1ClinicalTrials.gov (NCT02143167) Resistance Training and Amino Pyridine in Multiple Sclerosis. U.S. National Institutes of Health.
REF 2Application of adaptive design and decision making to a phase II trial of a phosphodiesterase inhibitor for the treatment of intermittent claudication. Trials. 2011; 12: 134.
REF 3Structure-activity relationships of (E)-3-(1,4-benzoquinonyl)-2-[(3-pyridyl)-alkyl]-2-propenoic acid derivatives that inhibit both 5-lipoxygenase and thromboxane A2 synthetase. J Med Chem. 1996 Aug 2;39(16):3148-57.
REF 4ClinicalTrials.gov (NCT01551381) Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of EV-077 in Type 2 Diabetic Subjects. U.S. National Institutes of Health.
REF 5Pharmacokinetic 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 6G 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 7Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017139)
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: 1964).
REF 9Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005013)
REF 10Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000441)
REF 11Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000225)
REF 12Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001597)
REF 13Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001438)
REF 14Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000262)
REF 15(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: 5175).
REF 16Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000420)
REF 17J Med Chem. 1986 May;29(5):816-9.Thromboxane synthetase inhibitors and antihypertensive agents. 2. N-[(1H-imidazol-1-yl)alkyl]-1H-isoindole-1,3(2H)-diones and N-[(1H-1,2,4-triazol-1-yl)alkyl]-1H-isoindole-1,3(2H)-diones as unique antihypertensive agents.
REF 18J Med Chem. 1981 Oct;24(10):1149-55.Highly selective inhibitors of thromboxane synthetase. 2. Pyridine derivatives.
REF 19J Med Chem. 2000 May 4;43(9):1841-51.1-imidazolyl(alkyl)-substituted di- and tetrahydroquinolines and analogues: syntheses and evaluation of dual inhibitors of thromboxane A(2) synthase and aromatase.
REF 20J Med Chem. 1985 Feb;28(2):164-70.Imidazo[1,5-a]pyridines: a new class of thromboxane A2 synthetase inhibitors.
REF 21Metabolic protection of the reperfused canine endocardium by the thromboxane synthetase inhibitor, dazoxiben. Prostaglandins Leukot Essent Fatty Acids. 1988 Jul;33(1):13-22.
REF 22RS-5186, a novel thromboxane synthetase inhibitor with a potent and extended duration of action. Thromb Res. 1988 Sep 1;51(5):507-20.
REF 23The novel phosphodiesterase inhibitor NM-702 improves claudication-limited exercise performance in patients with peripheral arterial disease. J Am Coll Cardiol. 2006 Dec 19;48(12):2539-45. Epub 2006Nov 28.
REF 24Nv-52: a novel thromboxane synthase inhibitor for the treatment of inflammatory bowel disease. Expert Opin Investig Drugs. 2007 Aug;16(8):1255-66.
REF 25Phase Ib single- and multiple-dose pharmacokinetic study of oral NV-52 in healthy volunteers. Drugs R D. 2008;9(3):159-66.
REF 26Pharmacological evaluation of combined PGI2 agonists/thromboxane synthase inhibitors, Bioorg. Med. Chem. Lett. 5(10):1087-1090 (1995).
REF 27Inhibition by FCE 22178 of platelet and glomerular thromboxane synthase in animal and human kidney disease. Adv Prostaglandin Thromboxane Leukot Res. 1991;21B:707-10.
REF 28Involvement of thromboxane A2, leukotrienes and free radicals in puromycin nephrosis in rats. Kidney Int. 1991 May;39(5):920-9.
REF 29Mechanisms of satigrel (E5510), a new anti-platelet drug, in inhibiting human platelet aggregation. Selectivity and potency against prostaglandin H synthases isozyme activities and phosphodiesterase isoform activities. Biol Pharm Bull. 1996 Jun;19(6):828-33.
REF 30Effects of the new class I antiarrhythmic agent Ro 22-9194, (2R)-2-amino-N-(2,6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide D-tartrate, on ischemia- and reperfusion-induced arrhythmias in dogs: involvement of thromboxane A2 synthase inhibitory activity. J Pharmacol Exp Ther. 1996 Nov;279(2):877-83.
REF 31A synthetic prostacyclin agonist with thromboxane synthase inhibitory activity, ONO-1301, protects myocardium from ischemia/reperfusion injury. Eur J Pharmacol. 2012 Jan 15;674(2-3):352-8.

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