Drug |
---|
show drug details
| PubChem ID: | 6434194 |
---|
Structure: |  |
---|
Synonyms: | (Z)-(3aR,4R,5R,6aS)-Hexahydro-5-hydroxy-4-((E)-(3S)-3-hydroxy-1-octenyl)-2H-cyclopenta(b)furan-delta(sup 2,delta)-valeric acid | 35121-78-9 | 6,9-alpha-Epoxy-11-alpha,15(S)-dihydroxyprosta-5(Z),13(E)-dien-1-oic acid | 63748-50-5 | 63859-31-4 | BRN 1690090 | C20H32O5 | Epoprostanol | Epoprostenol | EPOPROSTENOL SODIUM | Epoprostenol [USAN:INN] | Epoprostenolum [INN-Latin] | Flolan | KB-IV-24 | LS-125828 | PDSP1_001721 | PDSP2_001704 | PGI(sub 2) | PGI2 | PGX | Prosta-5,13-dien-1-oic acid, 6,9-epoxy-11,15-dihydroxy-, | Prosta-5,13-dien-1-oic acid, 6,9-epoxy-11,15-dihydroxy-, (5Z,9-alpha,11-alpha,13E,15S)- | Prosta-5,13-dien-1-oic acid, 6,9-epoxy-11,15-dihydroxy-, (5Z,9alpha,11alpha,13E,15S)- | Prostacyclin | Prostacyclins | Prostaglandin I | Prostaglandin I(2) | Prostaglandin I2 | Prostaglandin X | Prostaglandins X | U 53,217 | Vasocyclin |
|
---|
ATC-Codes: | |
---|
|
Target |
---|
show target details
| Uniprot ID: | CP2C9_HUMAN |
---|
Synonyms: | (R)-limonene 6-monooxygenase | (S)-limonene 6-monooxygenase | (S)-limonene 7-monooxygenase | CYPIIC9 | Cytochrome P450 2C9 | P-450MP | P450 MP-4/MP-8 | P450 PB-1 | S-mephenytoin 4-hydroxylase |
|
---|
EC-Numbers: | 1.14.13.48 1.14.13.49 1.14.13.80
|
---|
Organism: | Homo sapiens Human
|
---|
PDB IDs: | 1OG2 1OG5 1R9O |
---|
Structure: |  1R9O |
---|
|
Binding Affinities:Ki: | Kd: | Ic 50: | Ec50/Ic50: |
---|
- | - | - | - |
References:15569819 Cytochrome P4502C9-derived epoxyeicosatrienoic acids induce the expression of cyclooxygenase-2 in endothelial cells.. U Ruth Michaelis; John R Falck; Ronald Schmidt; Rudi Busse; Ingrid Fleming (2005) Arteriosclerosis, thrombosis, and vascular biology display abstractOBJECTIVE: Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs). CYP2C9-derived EETs elicit endothelial cell proliferation and angiogenesis, but the signaling pathways involved are incompletely understood. Because cyclooxygenase-2 (COX-2) is involved in angiogenesis, we determined whether a link exists between CYP2C9 and COX-2 expression. METHODS AND RESULTS: Human umbilical vein endothelial cells were infected with CYP2C9 sense or antisense adenoviral constructs. Overexpression of CYP2C9 increased COX-2 promoter activity, an effect accompanied by a significant increase in COX-2 protein expression and elevated prostacyclin production. The CYP2C9-induced expression of COX-2 was inhibited by the CYP2C9 inhibitor, sulfaphenazole, whereas 11,12-EET increased COX-2 expression. Overexpression of CYP2C9 and stimulation with 11,12-EET increased intracellular cAMP levels and stimulated DNA-binding of the cAMP-response element-binding protein. The protein kinase A inhibitor, KT5720, attenuated the CYP2C9-induced increase in COX-2 promoter activity and protein expression. Overexpression of CYP2C9 stimulated endothelial tube formation, an effect that was attenuated by the COX-2 inhibitor celecoxib. Identical responses were observed in cells preconditioned by cyclic strain to increase CYP2C expression. CONCLUSIONS: These data indicate that CYP2C9-derived EETs induce the expression of COX-2 in endothelial cells via a cAMP-dependent pathway and that this mechanism contributes to CYP2C9-induced angiogenesis. Overexpression of cytochrome P450 (CYP) 2C9 in endothelial cells increased cAMP levels, stimulated the cAMP-response element-binding protein, and enhanced cyclooxygenase-2 (COX-2) promoter activity, protein expression, and prostacyclin production. CYP2C9 overexpression stimulated endothelial tube formation, which was attenuated by the COX-2 inhibitor celecoxib. Thus, COX-2 contributes to CYP2C9-induced angiogenesis. |
|