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Drug-Target Interaction

Drug

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PubChem ID:6436247
Structure:
Synonyms:
70563-58-5
AC1O5LAW
AIDS-071761
AIDS071761
Antibiotic Tan 420F
CID6436247
Geldanamycin, 17-demethoxy-15-methoxy-11-O-methyl-, (15R)-
Herbimycin
Herbimycin A
LS-71126
NSC 305978
NSC305978
[(2R,3S,5S,6R,7S,8E,10S,11S,12E,14E)-2,5,6,11-tetramethoxy-3,7,9,15-tetram

Target

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Uniprot ID:PGH2_HUMAN
Synonyms:
COX-2
Cyclooxygenase-2
PGH synthase 2
PGHS-2
PHS II
Prostaglandin G/H synthase 2
Prostaglandin H2 synthase 2
Prostaglandin-endoperoxide synthase 2
EC-Numbers:1.14.99.1
Organism:Homo sapiens
Human
PDB IDs:1V0X
Structure:
1V0X

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----

References:

10535705
Tyrosine kinase inhibitors block the glucocorticoid stimulation of prostaglandin endoperoxide H synthase expression in amnion cells.. T Zakar; J E Mijovic; D Bhardwaj; D M Olson (1999) Canadian journal of physiology and pharmacology display abstract
Human amnion cells in primary culture respond to glucocorticoids in a characteristic fashion by the increased expression of the inducible prostaglandin endoperoxide H synthase isoenzyme, PGHS-2. Since PGHS-2 induction by agonists generally involves tyrosine kinases, we examined the possibility that the glucocorticoid stimulation of PGHS-2 in the amnion cells is tyrosine kinase dependent. PGHS-2 expression was stimulated in confluent, serum-starved amnion cells with dexamethasone, and the effect of the tyrosine kinase inhibitors herbimycin A and tyrphostins AG126, AG1288, and A1 on enzyme activity induction was determined. All four inhibitors blocked the increase of PGHS activity in a concentration-dependent manner with IC50 values of 0.077 +/- 0.05, 15.38 +/- 5.14, 20.91 +/- 3.1, and 29.77 +/- 8.21 microM, respectively (mean +/- SE, n = 4). Dexamethasone increased (approximately twofold) the tyrosine phosphorylation of 120-, 110-, and 77-kDa proteins in cell extracts, and herbimycin A selectively blocked the phosphorylation of the 110-kDa phosphoprotein. The stimulation of the steady-state level of PGHS-2 mRNA by dexamethasone was also inhibited by herbimycin A. These results suggest that glucocorticoids induce PGHS-2 expression in amnion cells with the involvement of tyrosine kinase(s). The role of tyrosine kinase dependent mechanisms in the control of amnion cell responsiveness to corticosteroids remains to be established.