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Drug-Target Interaction

Drug

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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

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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 abstract
OBJECTIVE: 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.