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Chemical Compound Review

Disopain     2-[3,4-bis(4-methoxyphenyl)- 1,2-oxazol-5...

Synonyms: mofezolac, Mofezolaco, Mofezolacum, Mofezolac (TN), CHEMBL259972, ...
 
 
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Disease relevance of mofezolac

  • When Apc gene knockout mice (APC1309 mice) were given 600 or 1200 p.p.m. mofezolac in their diet for 8 weeks, the numbers of intestinal polyps were also dose-dependently decreased, with reduction to 59% of that in the control diet group at the higher dose [1].
  • Administration of 300 ppm mofezolac plus 200 ppm nimesulide also significantly decreased polyp area in the intestine by 30% [2].
  • In contrast, COX activity in primary and consecutively cultured synovial cells isolated from osteoarthritis (OA) or normal arthritis was inhibited by NS-398, but not by mofezolac [3].
  • In the present study, we therefore investigated the effects of mofezolac on colon cancer development [4].
  • Treatment with 1200 ppm mofezolac significantly reduced the incidence, multiplicity and volume of colon carcinomas to 79%, 2.15 +/- 1.65 and 7.5 +/- 11.8 mm(3), respectively, compared with 94%, 3.19 +/- 1.87 and 23.7 +/- 31.2 mm(3) in the AOM treatment alone [4].
 

High impact information on mofezolac

  • The animals were treated with 300 or 600 ppm mofezolac (a COX-1 selective inhibitor) alone, 200 or 400 ppm nimesulide (a COX-2 selective inhibitor) alone, 300 ppm mofezolac plus 200 ppm nimesulide, 600 ppm mofezolac plus 400 ppm nimesulide, or 10 ppm indomethacin (a dual-COX inhibitor) in the diet from 7 weeks of age for 4 weeks [2].
  • Inhibitory effects of mofezolac, a cyclooxygenase-1 selective inhibitor, on intestinal carcinogenesis [1].
  • We therefore investigated whether a COX-1 selective inhibitor, mofezolac, suppresses intestinal carcinogenesis in rodents [1].
  • RESULTS: In normal rat, administration of indomethacin, relatively cyclooxygenase-1-selective inhibitor, mofezolac, or cyclooxygenase-2-selective inhibitors, NS-398 and JTE-522 had no effects on the escape latency against thermal stimuli [5].
  • Since IL-1ra suppresses the function of IL-1, a pro-inflammatory cytokine, the stimulatory effect of such NSAIDs as mofezolac on IL-1ra production could also be one of the mechanisms involved in its anti-inflammatory and antinociceptive actions [6].
 

Chemical compound and disease context of mofezolac

 

Anatomical context of mofezolac

  • Pharmacological experiments using mofezolac, a preferential inhibitor against COX-1, and NS-398, a selective inhibitor against COX-2, confirmed the involvement of COX-1 derived PGs in the induction of c-fos expression in the hind brain following the noxious stimulation [7].
 

Associations of mofezolac with other chemical compounds

 

Gene context of mofezolac

  • These data thus indicate that potent analgesic activity of mofezolac against the present model to be more closely related to its potent inhibitory activity against COX-1 but not against COX-2 [8].
  • These results confirm that COX-1, as well as COX-2, contributes to colon carcinogenesis and that mofezolac may be a good chemopreventive agent for human colon cancer [4].
  • Oral administration of mofezolac, a non-steroidal anti-inflammatory drug which potently inhibits COX-1, suppressed the PQ-induced writhing and peritoneal accumulation of PGs without affecting mRNA expression for both COX isoforms in mice [9].
 

Analytical, diagnostic and therapeutic context of mofezolac

References

  1. Inhibitory effects of mofezolac, a cyclooxygenase-1 selective inhibitor, on intestinal carcinogenesis. Kitamura, T., Kawamori, T., Uchiya, N., Itoh, M., Noda, T., Matsuura, M., Sugimura, T., Wakabayashi, K. Carcinogenesis (2002) [Pubmed]
  2. Combined effects of cyclooxygenase-1 and cyclooxygenase-2 selective inhibitors on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice. Kitamura, T., Itoh, M., Noda, T., Matsuura, M., Wakabayashi, K. Int. J. Cancer (2004) [Pubmed]
  3. Induction of cyclooxygenase-1 in cultured synovial cells isolated from rheumatoid arthritis patients. Onodera, M., Horiuchi, Y., Nakahama, K., Muneta, T., Mano, Y., Morita, I. Inflamm. Res. (2004) [Pubmed]
  4. Suppression of azoxymethane-induced colon cancer development in rats by a cyclooxygenase-1 selective inhibitor, mofezolac. Niho, N., Kitamura, T., Takahashi, M., Mutoh, M., Sato, H., Matsuura, M., Sugimura, T., Wakabayashi, K. Cancer Sci. (2006) [Pubmed]
  5. Participation of cyclooxygenases in cutaneous thermal nociception under non-inflamed and inflamed conditions. Suzuki, M., Hayash, I., Nara, Y., Kumaga, Y., Okamoto, H., Hoka, S., Majima, M. Inflamm. Res. (2001) [Pubmed]
  6. Effects of nonsteroidal anti-inflammatory drugs on interleukin-1 receptor antagonist production in cultured human peripheral blood mononuclear cells. Kusuhara, H., Matsuyuki, H., Okumoto, T. Prostaglandins (1997) [Pubmed]
  7. Principal involvement of cyclooxygenase-1-derived prostaglandins in the c-fos expression of the rat hind brain following visceral stimulation with acetic acid. Kusuhara, H., Fukunari, A., Matsuyuki, H., Okumoto, T. Brain Res. Mol. Brain Res. (1997) [Pubmed]
  8. Analgesic effect of mofezolac, a non-steroidal anti-inflammatory drug, against phenylquinone-induced acute pain in mice. Goto, K., Ochi, H., Yasunaga, Y., Matsuyuki, H., Imayoshi, T., Kusuhara, H., Okumoto, T. Prostaglandins Other Lipid Mediat. (1998) [Pubmed]
  9. Involvement of prostaglandins produced by cyclooxygenase-1 in murine visceronociception induced by phenylquinone. Kusuhara, H., Matsuyuki, H., Okumoto, T. Prostaglandins Other Lipid Mediat. (1998) [Pubmed]
  10. Mutagenicity tests of mofezolac (N-22). Ohuchida, A., Furukawa, A. The Journal of toxicological sciences. (1990) [Pubmed]
  11. Acute toxicity tests of mofezolac (N-22) in mice and rats. Satoh, K., Yamamoto, N., Kuwasaki, E., Ichiki, T., Sone, H., Kodama, R., Kuwata, M., Yamashita, K. The Journal of toxicological sciences. (1990) [Pubmed]
 
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