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Chemical Compound Review

Tocris-0942     N-(2-cyclohexyloxy-4-nitro...

Synonyms: CHEMBL7162, SureCN214213, CCRIS 8523, N194_SIGMA, ns-398, ...
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Disease relevance of ns-398


Psychiatry related information on ns-398


High impact information on ns-398

  • The effect is inhibited by antibodies to combinations of angiogenic factors, by NS-398 (a selective COX-2 inhibitor), and by aspirin [8].
  • The selective COX 2 inhibitor NS-398 and the dual COX 1/COX 2 inhibitor indomethacin inhibited inflammation at 2 hours but significantly exacerbated inflammation at 48 hours [9].
  • PGE(2) levels were determined in supernatants from epithelial cells treated with the selective COX-2 inhibitor NS-398, proinflammatory cytokines (interleukin 1beta and tumor necrosis factor-alpha), and conditioned medium from fibroblast cultures (both unstimulated and stimulated with proinflammatory cytokines) [10].
  • The addition of exogenous PGE(2) reversed the antiproliferative effect of NS-398 on Barrett's esophageal epithelial cells [10].
  • Par-4 levels were increased in cells treated with COX inhibitors such as NS-398, nimesulide, SC-58125, and sulindac sulfide [11].

Chemical compound and disease context of ns-398


Biological context of ns-398


Anatomical context of ns-398


Associations of ns-398 with other chemical compounds

  • We investigated the relationship between suppression of inflammation by COX-2 inhibitors (NS-398, nimesulide, DuP697, and etodolac) and their effects on gastric prostaglandin synthesis [24].
  • Administration of two unrelated COX-2 selective inhibitors (NS-398 and celecoxib) 24 h after ischemic PC abolished the ischemic PC-induced increase in tissue levels of PGE(2) and 6-keto-PGF(1alpha) [3].
  • However, addition of PGE(2) to cultures containing both GDF-9 and NS-398 overrides the NS-398 block in progesterone synthesis [25].
  • LPS-induced PGE2 and thromboxane B2 (TXB2) production in aspirin-treated neutrophils was significantly inhibited by IL-10, IL-4, and NS-398 [26].
  • We also observed that systemic administration of NS-398 decreased PDT induction of both PGE2 and vascular endothelial growth factor in treated RIF tumors [5].

Gene context of ns-398


Analytical, diagnostic and therapeutic context of ns-398

  • COX proteins were detected by Western blot analysis, and COX activity was determined in the presence or absence of NS-398, a specific COX-2 antagonist [1].
  • We evaluated the effect of cyclooxygenase (COX) inhibitors (NSAIDs) on human colon carcinoma cells (HCA-7) and identified several genes that are regulated after treatment with NS-398, a selective COX-2 inhibitor [11].
  • In response to pulses of acid or bile salts in an ex vivo organ culture system, COX-2 expression increased significantly in BE tissues, and this effect was attenuated by the selective COX-2 inhibitor NS-398 [29].
  • NS-398 was able to reduce the proliferation of monolayer cell cultures, as well as the growth of spheroids and tumor cell migration, in a dose-dependent manner [30].
  • NS-398 did not have an inhibitory effect on tumor invasion in the coculture spheroid system [30].


  1. Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice. Mizuno, H., Sakamoto, C., Matsuda, K., Wada, K., Uchida, T., Noguchi, H., Akamatsu, T., Kasuga, M. Gastroenterology (1997) [Pubmed]
  2. Cyclooxygenase-2 gene disruption attenuates the severity of acute pancreatitis and pancreatitis-associated lung injury. Ethridge, R.T., Chung, D.H., Slogoff, M., Ehlers, R.A., Hellmich, M.R., Rajaraman, S., Saito, H., Uchida, T., Evers, B.M. Gastroenterology (2002) [Pubmed]
  3. Cyclooxygenase-2 mediates the cardioprotective effects of the late phase of ischemic preconditioning in conscious rabbits. Shinmura, K., Tang, X.L., Wang, Y., Xuan, Y.T., Liu, S.Q., Takano, H., Bhatnagar, A., Bolli, R. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  4. Aspirin and NS-398 inhibit hepatocyte growth factor-induced invasiveness of human hepatoma cells. Abiru, S., Nakao, K., Ichikawa, T., Migita, K., Shigeno, M., Sakamoto, M., Ishikawa, H., Hamasaki, K., Nakata, K., Eguchi, K. Hepatology (2002) [Pubmed]
  5. Cyclooxygenase-2 inhibitor treatment enhances photodynamic therapy-mediated tumor response. Ferrario, A., Von Tiehl, K., Wong, S., Luna, M., Gomer, C.J. Cancer Res. (2002) [Pubmed]
  6. A cyclooxygenase-2 inhibitor attenuates spontaneous and TNF-alpha-induced non-rapid eye movement sleep in rabbits. Yoshida, H., Kubota, T., Krueger, J.M. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2003) [Pubmed]
  7. Intrathecal administration of a cylcooxygenase-1, but not a cyclooxygenase-2 inhibitor, reverses the effects of laparotomy on exploratory activity in rats. Martin, T.J., Buechler, N.L., Eisenach, J.C. Anesth. Analg. (2006) [Pubmed]
  8. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Tsujii, M., Kawano, S., Tsuji, S., Sawaoka, H., Hori, M., DuBois, R.N. Cell (1998) [Pubmed]
  9. Inducible cyclooxygenase may have anti-inflammatory properties. Gilroy, D.W., Colville-Nash, P.R., Willis, D., Chivers, J., Paul-Clark, M.J., Willoughby, D.A. Nat. Med. (1999) [Pubmed]
  10. The effect of selective cyclooxygenase-2 inhibition in Barrett's esophagus epithelium: an in vitro study. Buttar, N.S., Wang, K.K., Anderson, M.A., Dierkhising, R.A., Pacifico, R.J., Krishnadath, K.K., Lutzke, L.S. J. Natl. Cancer Inst. (2002) [Pubmed]
  11. Par-4, a proapoptotic gene, is regulated by NSAIDs in human colon carcinoma cells. Zhang, Z., DuBois, R.N. Gastroenterology (2000) [Pubmed]
  12. Tumor radiosensitization by antiinflammatory drugs: evidence for a new mechanism involving the oxygen effect. Crokart, N., Radermacher, K., Jordan, B.F., Baudelet, C., Cron, G.O., Grégoire, V., Beghein, N., Bouzin, C., Feron, O., Gallez, B. Cancer Res. (2005) [Pubmed]
  13. Expression of cyclooxygenase 2 in human malignant melanoma. Denkert, C., Köbel, M., Berger, S., Siegert, A., Leclere, A., Trefzer, U., Hauptmann, S. Cancer Res. (2001) [Pubmed]
  14. Involvement of 85-kd cytosolic phospholipase A(2) and cyclooxygenase-2 in the proliferation of human cholangiocarcinoma cells. Wu, T., Han, C., Lunz, J.G., Michalopoulos, G., Shelhamer, J.H., Demetris, A.J. Hepatology (2002) [Pubmed]
  15. Cyclooxygenase-2-derived prostaglandin E2 and lipoxin A4 accelerate resolution of allergic edema in Angiostrongylus costaricensis-infected rats: relationship with concurrent eosinophilia. Bandeira-Melo, C., Serra, M.F., Diaz, B.L., Cordeiro, R.S., Silva, P.M., Lenzi, H.L., Bakhle, Y.S., Serhan, C.N., Martins, M.A. J. Immunol. (2000) [Pubmed]
  16. Anti-inflammatory potency of FR167653, a p38 mitogen-activated protein kinase inhibitor, in mouse models of acute inflammation. Nishikori, T., Irie, K., Suganuma, T., Ozaki, M., Yoshioka, T. Eur. J. Pharmacol. (2002) [Pubmed]
  17. P53-mediated induction of Cox-2 counteracts p53- or genotoxic stress-induced apoptosis. Han, J.A., Kim, J.I., Ongusaha, P.P., Hwang, D.H., Ballou, L.R., Mahale, A., Aaronson, S.A., Lee, S.W. EMBO J. (2002) [Pubmed]
  18. Mechanism of radiation-induced bystander effect: role of the cyclooxygenase-2 signaling pathway. Zhou, H., Ivanov, V.N., Gillespie, J., Geard, C.R., Amundson, S.A., Brenner, D.J., Yu, Z., Lieberman, H.B., Hei, T.K. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  19. Cyclooxygenase-2 is required for tumor necrosis factor-alpha- and angiotensin II-mediated proliferation of vascular smooth muscle cells. Young, W., Mahboubi, K., Haider, A., Li, I., Ferreri, N.R. Circ. Res. (2000) [Pubmed]
  20. Influence of coenzyme A-independent transacylase and cyclooxygenase inhibitors on the proliferation of breast cancer cells. Trimboli, A.J., Waite, B.M., Atsumi, G., Fonteh, A.N., Namen, A.M., Clay, C.E., Kute, T.E., High, K.P., Willingham, M.C., Chilton, F.H. Cancer Res. (1999) [Pubmed]
  21. Selective inhibition of cyclooxygenase-2 suppresses growth and induces apoptosis in human esophageal adenocarcinoma cells. Souza, R.F., Shewmake, K., Beer, D.G., Cryer, B., Spechler, S.J. Cancer Res. (2000) [Pubmed]
  22. Transcription factor Nrf2 regulates inflammation by mediating the effect of 15-deoxy-Delta(12,14)-prostaglandin j(2). Itoh, K., Mochizuki, M., Ishii, Y., Ishii, T., Shibata, T., Kawamoto, Y., Kelly, V., Sekizawa, K., Uchida, K., Yamamoto, M. Mol. Cell. Biol. (2004) [Pubmed]
  23. Angiogenic effects of prostaglandin E2 are mediated by up-regulation of CXCR4 on human microvascular endothelial cells. Salcedo, R., Zhang, X., Young, H.A., Michael, N., Wasserman, K., Ma, W.H., Martins-Green, M., Murphy, W.J., Oppenheim, J.J. Blood (2003) [Pubmed]
  24. Cyclooxygenase 1 contributes to inflammatory responses in rats and mice: implications for gastrointestinal toxicity. Wallace, J.L., Bak, A., McKnight, W., Asfaha, S., Sharkey, K.A., MacNaughton, W.K. Gastroenterology (1998) [Pubmed]
  25. Growth differentiation factor-9 stimulates progesterone synthesis in granulosa cells via a prostaglandin E2/EP2 receptor pathway. Elvin, J.A., Yan, C., Matzuk, M.M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  26. Regulation by interleukin-10 and interleukin-4 of cyclooxygenase-2 expression in human neutrophils. Niiro, H., Otsuka, T., Izuhara, K., Yamaoka, K., Ohshima, K., Tanabe, T., Hara, S., Nemoto, Y., Tanaka, Y., Nakashima, H., Niho, Y. Blood (1997) [Pubmed]
  27. Cyclooxygenase-1 is up-regulated in cervical carcinomas: autocrine/paracrine regulation of cyclooxygenase-2, prostaglandin e receptors, and angiogenic factors by cyclooxygenase-1. Sales, K.J., Katz, A.A., Howard, B., Soeters, R.P., Millar, R.P., Jabbour, H.N., Soeters, R.P. Cancer Res. (2002) [Pubmed]
  28. Cyclooxygenase-2 inhibits tumor necrosis factor alpha-mediated apoptosis in renal glomerular mesangial cells. Ishaque, A., Dunn, M.J., Sorokin, A. J. Biol. Chem. (2003) [Pubmed]
  29. Cyclooxygenase 2 expression in Barrett's esophagus and adenocarcinoma: Ex vivo induction by bile salts and acid exposure. Shirvani, V.N., Ouatu-Lascar, R., Kaur, B.S., Omary, M.B., Triadafilopoulos, G. Gastroenterology (2000) [Pubmed]
  30. Expression of cyclooxygenase 2 (COX-2) in human glioma and in vitro inhibition by a specific COX-2 inhibitor, NS-398. Joki, T., Heese, O., Nikas, D.C., Bello, L., Zhang, J., Kraeft, S.K., Seyfried, N.T., Abe, T., Chen, L.B., Carroll, R.S., Black, P.M. Cancer Res. (2000) [Pubmed]
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