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CYP5A1

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 1353

Nomenclature: CYP5A1

Abbreviated Name: Thromboxane-A synthase

Family: CYP5, CYP7 and CYP8 families, Prostaglandin synthases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 533 7q34 TBXAS1 thromboxane A synthase 1
Mouse 4 533 6 17.85 cM Tbxas1 thromboxane A synthase 1, platelet
Rat 4 533 4q22 Tbxas1 thromboxane A synthase 1
Previous and Unofficial Names Click here for help
CYP5 | cytochrome P450, family 5, subfamily A, polypeptide 1 | cytochrome P450 5A1 | thromboxane A synthase 1 | thromboxane A synthase 1, platelet | thromboxane A synthase 1 (platelet)
Database Links Click here for help
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ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
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Enzyme Reaction Click here for help
EC Number: 5.3.99.5 PGH2 = thromboxane A2

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 10a [PMID: 1447738] Small molecule or natural product Hs Inhibition 8.7 pIC50 1
pIC50 8.7 (IC50 2x10-9 M) [1]
dazoxiben Small molecule or natural product Hs Inhibition 8.5 pIC50 9
pIC50 8.5 [9]
ozagrel Small molecule or natural product Approved drug Immunopharmacology Ligand Hs Inhibition 8.2 – 8.4 pIC50 6-7
pIC50 8.4 (IC50 4x10-9 M) [7]
Description: Inhibition of thromboxane A2 synthetase activity in human washed platelets.
pIC50 8.2 (IC50 6x10-9 M) [6]
Description: Inhibition of TXAB2 synthesis by microsome of human platelets.
furegrelate sodium Small molecule or natural product Hs Inhibition 7.8 pIC50 3
pIC50 7.8 [3]
compound 7p [PMID: 7861416] Small molecule or natural product Click here for species-specific activity table Hs Inhibition <5.0 pIC50 2
pIC50 <5.0 (IC50 >1x10-5 M) [2]
picotamide Small molecule or natural product Hs Inhibition 3.8 pIC50 4
pIC50 3.8 [4]
camonagrel Small molecule or natural product Hs Inhibition - - 5
[5]
Immunopharmacology Comments
The arachadonic acid-derived inflammtory mediators leukotrienes, prostaglandins, and thromboxanes play important roles in inflammatory and allergic diseases, so the search for inhibitors of their production is a long-standing medicinal chemistry goal [8]. The most well known drug family in this field are the cyclooxygenase (COX) Inhibitors (or nonsteroidal antiinflammatory drugs; NSAIDs) which reduce prostaglandin synthesis, and are widely used for their antiinflammatory action. The clinically approved 5-lipoxygenase (5-LOX) inhibitor zileuton blocks formation of leukotrienes. The thromboxane A2 synthetase function of CYP5A1 is another valid molecular target in this search for novel antiinflammatory drugs. The discovery of inhibitors of thromboxane synthesis may help address those conditions that do not respond to inhibitors of the prostanoid and leukotriene pathways.

References

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1. Bhagwat SS, Gude C, Boswell C, Contardo N, Cohen DS, Dotson R, Mathis J, Lee W, Furness P, Zoganas H. (1992) Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 4. 8-[[(4-Chlorophenyl)sulfonyl]amino]-4-(3-(3-pyridinyl) propyl)octanoic acid and analogs. J Med Chem, 35 (23): 4373-83. [PMID:1447738]

2. Faull AW, Brewster AG, Brown GR, Smithers MJ, Jackson R. (1995) Dual-acting thromboxane receptor antagonist/synthase inhibitors: synthesis and biological properties of [2-substituted-4-(3-pyridyl)-1,3-dioxan-5-yl] alkenoic acids. J Med Chem, 38 (4): 686-94. [PMID:7861416]

3. Gorman RR, Johnson RA, Spilman CH, Aiken JW. (1983) Inhibition of platelet thromboxane A2 synthase activity by sodium 5-(3'-pyridinylmethyl)benzofuran-2-carboxylate. Prostaglandins, 26 (2): 325-42. [PMID:6316421]

4. Gresele P, Deckmyn H, Arnout J, Nenci GG, Vermylen J. (1989) Characterization of N,N'-bis(3-picolyl)-4-methoxy-isophtalamide (picotamide) as a dual thromboxane synthase inhibitor/thromboxane A2 receptor antagonist in human platelets. Thromb Haemost, 61 (3): 479-84. [PMID:2552606]

5. Gryglewski RJ, Szczeklik A, Korbut R, Swies J, Musiał J, Krzanowski M, Maga P. (1995) The mechanism of anti-thrombotic, thrombolytic and fibrinolytic actions of camonagrel--a new thromboxane synthase inhibitor. Wien Klin Wochenschr, 107 (9): 283-9. [PMID:7778318]

6. Hibi S, Okamoto Y, Tagami K, Numata H, Kobayashi N, Shinoda M, Kawahara T, Harada K, Miyamoto K, Yamatsu I. (1996) 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, 39 (16): 3148-57. [PMID:8759636]

7. Hiraku S, Taniguchi K, Wakitani K, Omawari N, Kira H, Miyamoto T, Okegawa T, Kawasaki A, Ujiie A. (1986) Pharmacological studies on the TXA2 synthetase inhibitor (E)-3-[p-(1H-imidazol-1-ylmethyl)phenyl]-2-propenoic acid (OKY-046). Jpn J Pharmacol, 41 (3): 393-401. [PMID:3093741]

8. Khanapure SP, Garvey DS, Janero DR, Letts LG. (2007) Eicosanoids in inflammation: biosynthesis, pharmacology, and therapeutic frontiers. Curr Top Med Chem, 7 (3): 311-40. [PMID:17305573]

9. Randall MJ, Parry MJ, Hawkeswood E, Cross PE, Dickinson RP. (1981) UK-37, 248, a novel, selective thromboxane synthetase inhibitor with platelet anti-aggregatory and anti-thrombotic activity. Thromb Res, 23 (1-2): 145-62. [PMID:6795753]

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