Profile of JTE : 522 as a Human Cyclooxygenase : 2 Inhibitor

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Author(s)

Abstract

Inhibitory activity and the mechanism of action of JTE-522 (4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide), a novel selective cyclooxygenase (COX)-2 inhibitor, on human COX-1 and COX-2 were investigated and compared with those of reference compounds. In an enzyme assay, JTE-522 inhibited yeast-expressed human recombinant COX-2 with an IC<SUB>50</SUB> value of 0.085 μM. In contrast, JTE-522 did not inhibit human COX-1 prepared from human platelets at concentrations up to 100 μM. In a cell-based assay, JTE-522 diminished lipopolysaccharide-induced prostaglandin E<SUB>2</SUB> production in human peripheral blood mononuclear cells (COX-2) (IC<SUB>50</SUB> value = 15.1 nM). On the other hand, JTE-522 was less potent at inhibiting calcium ionophore-induced thromboxane B<SUB>2</SUB> production in washed human platelets (COX-1) (IC<SUB>50</SUB> value = 6210 nM). JTE-522 showed highly selective inhibition of human COX-2, and its activity was more selective than that of other COX-2 inhibitors (NS-398 and SC-58635). Human recombinant COX-2 activity was attenuated by JTE-522 in a dose-dependent and time-dependent manner. In contrast, the inhibitory activity of JTE-522 on human COX-1 was not affected by preincubation time. COX-2 inhibition by JTE-522 could not be recovered by gel filtration. These results indicate that JTE-522 is a highly selective, time-dependent and irreversible inhibitor of human COX-2.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 78(3), 365-371, 1998-11-01

    The Japanese Pharmacological Society

References:  29

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008681395
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4610826
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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