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

• Suppression of azoxymethane-induced colon cancer development in rats by a cyclooxygenase-1 selective inhibitor, mofezolac [4].

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

• The effects of nonsteroidal anti-inflammatory drugs (NSAIDs), mofezolac, indomethacin, sodium diclofenac, and zaltoprofen, on the production of interleukin-1 receptor antagonist (IL-1ra) were examined in cultured human peripheral blood mononuclear cells (PBMC) [6].
• Among the NSAIDs tested, mofezolac and sodium diclofenac were found to stimulate the mRNA expression for IL-1ra without affecting the mRNA expression for IL-1 beta [6].

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

• Mutagenicity tests of mofezolac (N-22) [10].
• Acute toxicity tests of mofezolac (N-22) in mice and rats [11].

References