Profile of JTE-522 as a Human Cyclooxygenase-2 Inhibitor.
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- Wakitani Korekiyo
- Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute
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- Nanayama Toyomichi
- Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute
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- Masaki Michiko
- Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute
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- Matsushita Mutsuyoshi
- Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute
Bibliographic Information
- Other Title
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- Profile of JTE-522 as a Human Cyclooxyg
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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 IC50 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 E2 production in human peripheral blood mononuclear cells (COX-2) (IC50 value = 15.1 nM). On the other hand, JTE-522 was less potent at inhibiting calcium ionophore-induced thromboxane B2 production in washed human platelets (COX-1) (IC50 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
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- The Japanese Journal of Pharmacology
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The Japanese Journal of Pharmacology 78 (3), 365-371, 1998
The Japanese Pharmacological Society
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Keywords
Details 詳細情報について
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- CRID
- 1390001204286083328
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- NII Article ID
- 10008681395
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- NII Book ID
- AA00691188
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- COI
- 1:CAS:528:DyaK1cXnslyktb8%3D
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- ISSN
- 13473506
- 00215198
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- NDL BIB ID
- 4610826
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- PubMed
- 9869271
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- Web Site
- https://ndlsearch.ndl.go.jp/books/R000000004-I4610826
- https://api.elsevier.com/content/article/PII:S0021519819310364?httpAccept=text/xml
- https://api.elsevier.com/content/article/PII:S0021519819310364?httpAccept=text/plain
- https://www.jstage.jst.go.jp/article/jjp/78/3/78_3_365/_pdf
- https://search.jamas.or.jp/link/ui/1999089404
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed