CYP5A1 | Prostaglandin synthases | IUPHAR/BPS Guide to PHARMACOLOGY

CYP5A1

Target id: 1353

Nomenclature: CYP5A1

Abbreviated Name: Thromboxane synthase

Family: CYP5, CYP7 and CYP8 families, Prostaglandin synthases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     CYP5A1 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - - TBXAS1 thromboxane A synthase 1
Mouse - - Tbxas1 thromboxane A synthase 1, platelet
Rat - - Tbxas1 thromboxane A synthase 1
Previous and Unofficial Names
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
BRENDA
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 5.3.99.5 PGH2 = thromboxane A2

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
compound 10a [PMID: 1447738] Hs Inhibition 8.7 pIC50 1
pIC50 8.7 (IC50 2x10-9 M) [1]
ozagrel Hs Inhibition 8.2 pIC50 3
pIC50 8.2 (IC50 6x10-9 M) [3]
Description: Inhibition of TXAB2 synthesis by microsome of human platelets.
compound 7p [PMID: 7861416] Hs Inhibition <5.0 pIC50 2
pIC50 <5.0 (IC50 >1x10-5 M) [2]
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 [4]. 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. 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]

4. 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]

How to cite this page

Prostaglandin synthases: CYP5A1. Last modified on 10/07/2018. Accessed on 19/09/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1353.