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A Novel Selective Prostaglandin E2 Synthesis Inhibitor Relieves Pyrexia and Chronic Inflammation in Rats

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Abstract

Prostaglandin E2 (PGE2) is a terminal prostaglandin in the cyclooxygenase (COX) pathway. Inhibition of PGE2 production may relieve inflammatory symptoms such as fever, arthritis, and inflammatory pain. We report here the profile of a novel selective PGE2 synthesis inhibitor, compound A [N-[(1S,3S)-3-carbamoylcyclohexyl]-1-(6-methyl-3-phenylquinolin-2-yl)piperidine-4-carboxamide], in animal models of pyrexia and inflammation. The compound selectively suppressed the synthesis of PGE2 in human alveolar adenocarcinoma cell line A549 cells and rat macrophages. In the lipopolysaccharide-induced pyrexia model, this compound selectively reduced PGE2 production in cerebrospinal fluid and showed an anti-pyretic effect. In the adjuvant-induced arthritis model, compound A therapeutically decreased foot swelling in the established arthritis. Our data demonstrates that selective suppression of PGE2 synthesis shows anti-pyretic and anti-inflammatory effects, suggesting that selective PGE2 synthesis inhibitors can be applied as an alternative treatment to nonsteroidal, anti-inflammatory drugs (NSAIDs) or COX-2-selective inhibitors.

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Acknowledgments

We are grateful to Miwako Takeuchi for her technical assistance.

Author information

Authors and Affiliations

  1. Cardiovascular-Metabolics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan

    Ryusuke Sugita

  2. Frontier Research Laboratories, Daiichi Sankyo Co., Ltd., Shinagawa R&D Center, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan

    Harumi Kuwabara, Kotaro Sugimoto & Kohei Shimada

  3. Biological Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan

    Kazufumi Kubota

  4. Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan

    Yuichiro Imamura

  5. Medical Chemistry Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan

    Toshihiro Kiho

  6. Venture Science Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan

    Atsushi Tengeiji

  7. Global Project Management Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan

    Katsuhiro Kawakami

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  1. Ryusuke Sugita
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  2. Harumi Kuwabara
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  4. Kazufumi Kubota
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  8. Katsuhiro Kawakami
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  9. Kohei Shimada
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Correspondence to Kohei Shimada.

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Sugita, R., Kuwabara, H., Sugimoto, K. et al. A Novel Selective Prostaglandin E2 Synthesis Inhibitor Relieves Pyrexia and Chronic Inflammation in Rats. Inflammation 39, 907–915 (2016). https://doi.org/10.1007/s10753-016-0323-5

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  • DOI: https://doi.org/10.1007/s10753-016-0323-5

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