Disease relevance of Cgp 28238

• Effect of flosulide, a selective cyclooxygenase 2 inhibitor, on passive heymann nephritis in the rat [1].
• Although 20 and its oxygen linkage analog 2 (flosulide) are equipotent in the in vitro assays, compound 20 is more potent in the rat paw edema assay, has a longer t1/2 in squirrel monkeys, and seems less ulcergenic than 2 in rats [2].
• Treatment with flosulide reduced the proteinuria to 26.1 +/- 9 mg/24 hr at 3 mg flosulide/kg body wt/day and 35.5 +/- 6 mg/24 hr at 9 mg/kg body wt/day, which was equivalent to a reduction of proteinuria by a maximum of 65% (P < 0.05) [1].
• Pretreatment with the cyclooxygenase-2 selective inhibitors DuP 697, flosulide and SC58125 also attenuated allodynia (by 80-100%) but had no effect on the development of oedema or mechanical hyperalgesia [3].
• METHODS: We assessed the gastrointestinal tolerability of flosulide (20 mg twice a day), a highly selective Cox-2 inhibitor with that of naproxen (500 mg twice a day), which has equal affinity for Cox-1 and -2 in 19 patients with osteoarthrosis in a randomized, double blind, crossover endoscopy study [4].

High impact information on Cgp 28238

• Available experimental and clinical data of selective COX-2 inhibitors, including flosulide, celecoxib or rofecoxib, suggest improved gastric tolerance as compared to conventional, non-selective NSAIDs [5].
• There was concentration-dependent (IC50 = 107 +/- 55 nM) and ultimately complete inhibition of PGE2 generation by flosulide [6].
• High-dose flosulide induced a decrease in glomerular prostanoid production possibly because of COX-1 inhibition [1].
• High-dose flosulide treatment reduced renal prostaglandin production and caused a marked decline in COX-1 and COX-2 protein expression [1].
• However, a 250-fold molar excess of flosulide could not displace labeled FMLP from the receptor [7].

Biological context of Cgp 28238

• We have shown that flosulide (6-(2,4-difluorophenoxy)-5-methylsulfonylamino-1-indanone ), a novel highly potent anti-inflammatory compound, inhibits superoxide production induced by N-formyl-Met-Leu-Phe (FMLP), C5a and PMA without impairing bacterial killing or chemotaxis [7].
• Acute effects of the anti-inflammatory cyclooxygenase-2 selective inhibitor, flosulide, on renal plasma flow and glomerular filtration rate in rats [8].

Anatomical context of Cgp 28238

• Influence of the anti-inflammatory compound flosulide on granulocyte function [7].
• Renal and endocrine effects of flosulide, after single and repeated administration to healthy volunteers [9].
• Changes in prostaglandin E2 (PGE2) levels in paw exudate, stomach and kidney of arthritic rats: effects of flosulide [10].

Associations of Cgp 28238 with other chemical compounds

• HN-56249 surpassed the COX-2 selectivities of the COX-2 selective inhibitors 3-cyclohexyloxy-4-methylsulfonylamino-nitrobenzene (NS-398) and 6-(2,4-difluorophenoxy)-5-methyl-sulfonylamino-1-indanone (flosulide) in the intact cell assays by eight- and threefold, respectively, and in the whole blood assays by approximately 40-fold [11].
• The TPA-induced increase in 6-keto-PGF1 alpha was greatly inhibited by all COX-2 inhibitors while LTB4 was potentiated by both flosulide and L-745,337 [12].
• The selective COX-2 inhibitor, flosulide, is significantly better tolerated and causes less gastric mucosal damage than naproxen when given for two weeks [13].
• Fourteen days after inoculation, AA rats were selected and treated orally every day for two weeks with the selective COX-2 inhibitor, flosulide, or the COX-1-COX-2 inhibitor, indomethacin [10].

Gene context of Cgp 28238

• CONCLUSIONS: Under the influence of flosulide, a highly COX-2-selective inhibitor, we observed an antiproteinuric drug effect [1].
• Substituted heterocyclic analogs as selective COX-2 inhibitors in the flosulide class [14].
• The topical effects of cyclooxygenase-2 (COX-2)-selective inhibitors, flosulide (CGP 28238), L-745,337 and SC-57,666 were examined in AA- and TPA-induced ear dermal inflammation in the mouse [12].
• Myeloperoxidase (MPO) levels were lowered by flosulide and L-745,337 but not by SC-57,666 [12].

Analytical, diagnostic and therapeutic context of Cgp 28238

• A good correlation between this in vitro effect and in vivo anti-inflammatory potency in rat adjuvant arthritis was found for flosulide and its metabolites [7].

References