General Information of Drug Therapeutic Target (DTT) (ID: TTKNWZ4)

DTT Name Thromboxane-A synthase (TBXAS1)
Synonyms Thromboxane A2 synthase; TXS; TXA synthase; Cytochrome P450 5A1; CYP5A1; CYP5
Gene Name TBXAS1
DTT Type
Clinical trial target
[1]
BioChemical Class
Intramolecular oxidoreductase
UniProt ID
THAS_HUMAN
TTD ID
T78356
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 5.3.99.5
Sequence
MEALGFLKLEVNGPMVTVALSVALLALLKWYSTSAFSRLEKLGLRHPKPSPFIGNLTFFR
QGFWESQMELRKLYGPLCGYYLGRRMFIVISEPDMIKQVLVENFSNFTNRMASGLEFKSV
ADSVLFLRDKRWEEVRGALMSAFSPEKLNEMVPLISQACDLLLAHLKRYAESGDAFDIQR
CYCNYTTDVVASVAFGTPVDSWQAPEDPFVKHCKRFFEFCIPRPILVLLLSFPSIMVPLA
RILPNKNRDELNGFFNKLIRNVIALRDQQAAEERRRDFLQMVLDARHSASPMGVQDFDIV
RDVFSSTGCKPNPSRQHQPSPMARPLTVDEIVGQAFIFLIAGYEIITNTLSFATYLLATN
PDCQEKLLREVDVFKEKHMAPEFCSLEEGLPYLDMVIAETLRMYPPAFRFTREAAQDCEV
LGQRIPAGAVLEMAVGALHHDPEHWPSPETFNPERFTAEARQQHRPFTYLPFGAGPRSCL
GVRLGLLEVKLTLLHVLHKFRFQACPETQVPLQLESKSALGPKNGVYIKIVSR
Function endoplasmic reticulum membrane, 12-hydroxyheptadecatrienoic acid synthase activity, thromboxane-A synthase activity, cyclooxygenase pathway, icosanoid metabolic process.
KEGG Pathway
Arachidonic acid metabolism (hsa00590 )
Metabolic pathways (hsa01100 )
Platelet activation (hsa04611 )
Reactome Pathway
Synthesis of Prostaglandins (PG) and Thromboxanes (TX) (R-HSA-2162123 )
Defective TBXAS1 causes GHDD (R-HSA-5579032 )
Eicosanoids (R-HSA-211979 )
BioCyc Pathway
MetaCyc:HS00728-MON

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
PYRIDINE DMF8CJ9 N. A. N. A. Phase 4 [1]
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6 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
NM-702 DMDJLY9 Angina pectoris BA40 Phase 3 [2]
E-6700 DMUWJI4 Asthma CA23 Phase 2 [3]
EV-077 DM1FCDH Type-2 diabetes 5A11 Phase 2 [4]
FK-070 DMJSD5W Angina pectoris BA40 Phase 2 [5]
G-619 DM3H6YC Thrombosis DB61-GB90 Phase 1 [6]
NV-52 DM0UOA9 Inflammatory bowel disease DD72 Phase 1 [7]
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⏷ Show the Full List of 6 Clinical Trial Drug(s)
6 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Satigrel DM4LSJ2 Thrombosis DB61-GB90 Discontinued in Preregistration [8]
Imitrodast DMQ2ULV Asthma CA23 Discontinued in Phase 2 [9]
MILACAINIDE TARTRATE DMJLNUD Cardiac arrhythmias BC9Z Discontinued in Phase 2 [10]
Rolafagrel DM8Q7XV Nephritis GB40 Discontinued in Phase 2 [11]
CGS-13080 DMUPKYO Asthma CA23 Terminated [13]
Dazoxiben DMJUW8H N. A. N. A. Terminated [14]
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⏷ Show the Full List of 6 Discontinued Drug(s)
1 Preclinical Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
ONO-1301 DMMBIHO Angina pectoris BA40 Preclinical [12]
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9 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
2-(10-Imidazol-1-yl-decyl)-isoindole-1,3-dione DMVXN01 Discovery agent N.A. Investigative [15]
2-(6-Imidazol-1-yl-hexyl)-isoindole-1,3-dione DMKI6GQ Discovery agent N.A. Investigative [15]
2-(8-Imidazol-1-yl-octyl)-isoindole-1,3-dione DMLQ9WD Discovery agent N.A. Investigative [15]
4-Methyl-pyridine DME6UOM Discovery agent N.A. Investigative [1]
5-(2-Imidazol-1-yl-ethyl)-7,8-dihydro-quinoline DMCP5U8 Discovery agent N.A. Investigative [16]
5-Imidazol-1-yl-5,6,7,8-tetrahydro-quinoline DMVSBHU Discovery agent N.A. Investigative [16]
6-Imidazol-1-yl-isoquinoline DMQXL1Y Discovery agent N.A. Investigative [16]
CV-6504.HCL DMO9WZN Discovery agent N.A. Investigative [17]
ONO-1581 DMSXT0H Discovery agent N.A. Investigative [18]
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⏷ Show the Full List of 9 Investigative Drug(s)

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Type 2 diabetes 5A11 Liver tissue 6.56E-01 0.02 0.08
Asthma CA23 Nasal and bronchial airway 1.71E-03 0.08 0.24
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References

1 Highly selective inhibitors of thromboxane synthetase. 2. Pyridine derivatives. J Med Chem. 1981 Oct;24(10):1149-55.
2 The 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.
3 Structure-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.
4 Company report (Pharmaceuticalintelligence)
5 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.
6 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.
7 Phase Ib single- and multiple-dose pharmacokinetic study of oral NV-52 in healthy volunteers. Drugs R D. 2008;9(3):159-66.
8 Mechanisms 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.
9 RS-5186, a novel thromboxane synthetase inhibitor with a potent and extended duration of action. Thromb Res. 1988 Sep 1;51(5):507-20.
10 Effects 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.
11 Inhibition by FCE 22178 of platelet and glomerular thromboxane synthase in animal and human kidney disease. Adv Prostaglandin Thromboxane Leukot Res. 1991;21B:707-10.
12 A 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.
13 Imidazo[1,5-a]pyridines: a new class of thromboxane A2 synthetase inhibitors. J Med Chem. 1985 Feb;28(2):164-70.
14 Metabolic protection of the reperfused canine endocardium by the thromboxane synthetase inhibitor, dazoxiben. Prostaglandins Leukot Essent Fatty Acids. 1988 Jul;33(1):13-22.
15 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-... J Med Chem. 1986 May;29(5):816-9.
16 1-imidazolyl(alkyl)-substituted di- and tetrahydroquinolines and analogues: syntheses and evaluation of dual inhibitors of thromboxane A(2) synthas... J Med Chem. 2000 May 4;43(9):1841-51.
17 Involvement of thromboxane A2, leukotrienes and free radicals in puromycin nephrosis in rats. Kidney Int. 1991 May;39(5):920-9.
18 Pharmacological evaluation of combined PGI2 agonists/thromboxane synthase inhibitors, Bioorg. Med. Chem. Lett. 5(10):1087-1090 (1995).