(−)-R-fenoprofen: Formation of fenoprofenyl-coenzyme A by rat liver microsomes

Benoît, Etienne; Delatour, P.; Olivier, Lisa M.; Caldwell, John

doi:10.1016/0006-2952(94)00417-k

Cited by 11 publications

(4 citation statements)

References 12 publications

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“…The effect of detergents on enzyme properties and inhibitor potencies is not a phenomenon unique to Cox [37][38][39][40]. The introduction of a micellar environment allows for the possibility of partitioning of substrate, enzyme or inhibitor into the micelle, as well as the potential for the specific interaction of detergent monomers with each componant.…”

Section: Discussionmentioning

confidence: 99%

Detergents profoundly affect inhibitor potencies against both cyclo-oxygenase isoforms

Ouellet

Falgueyret

Percival

2004

Biochemical Journal

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The sensitivity of Coxs (cyclo-oxygenases) to inhibition is known to be highly dependent on assay conditions. In the present study, the inhibitor sensitivities of purified Cox-1 and -2 were determined in a colorimetric assay using the reducing agent N, N, N ', N '-tetramethyl- p -phenylenediamine. With the detergent genapol X-100 (2 mM) present, the potencies of nimesulide, ibuprofen, flufenamic acid, niflumic acid and naproxen were increased over 100-fold against Cox-2 and titration curve shapes changed, so that maximal inhibition now approached 100%. Indomethacin, diclofenac and flosulide were not changed in potency. Similar effects of genapol were observed with inhibitors of Cox-1. DuP-697 and two analogues became more than 10-fold less potent against Cox-2 with genapol present. Tween-20, Triton X-100 and phosphatidylcholine, but not octylglucoside, gave qualitatively similar effects as genapol. Similar detergent-dependent changes in inhibitor potency were also observed using a [(14)C]arachidonic acid HPLC assay. The increases in potency of ibuprofen, flufenamic acid, isoxicam and niflumic acid towards Cox-2 and ibuprofen towards Cox-1 were accompanied by a change from time-independent to time-dependent inhibition. The interactions of Cox inhibitors has been described in terms of multiple binding step mechanisms. The genapol-dependent increase in inhibitor potency for ketoprofen was associated with an increase in the rate constant for the conversion of the initial enzyme-inhibitor complex to a second, more tightly bound form. The loss of potency for some inhibitors is probably due to inhibitor partitioning into detergent micelles. The present study identifies detergents as another factor that must be considered when determining inhibitor potencies against both Cox isoforms.

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Section: Discussionmentioning

confidence: 99%

Detergents profoundly affect inhibitor potencies against both cyclo-oxygenase isoforms

Ouellet

Falgueyret

Percival

2004

Biochemical Journal

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“…Interestingly, palmitic acid at all doses investigated significantly increased the inversion ratio of ibuprofen, contradictory to all of the previous reports. [29][30][31] This contradictory result should not indicate that the different enzyme was involved, because the LACS activity in Caco-2 cells had been testified, 14) and the LACS5 isoform which metabolizes the palmitic acid efficiently was predominantly and strongly expressed in intestinal epithelial cells. 32,33) It is useful to emphasize that the much longer time entailed in the present investigation compared to previous research may explain such a reversal result.…”

Section: Figmentioning

confidence: 99%

Unidirectional Inversion of Ibuprofen in Caco-2 Cells: Developing a Suitable Model for Presystemic Chiral Inversion Study

Hao

Wang

Ding

et al. 2005

Biological & Pharmaceutical Bulletin

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“…21 AE-Fenoprofenoyl-CoA 7, AE-flurbiprofenoyl-CoA 8, and S-ketoprofenoyl-CoA 9 were synthesized, as these 2-APAs undergo chiral inversion in vivo. 2,3,8,10 S-Naproxenoyl-CoA 10 was also synthesized, as it is structurally related but its chiral inversion in vivo is reported to be extremely limited. 11 The 2-APAs reacted with carbonyl diimidazole 20,22 to form the acyl-imidazole intermediates, the presence of which was confirmed by 1 H NMR.…”

mentioning

confidence: 99%

“…Chiral inversion probably occurs in both directions, with stereoselective formation of the CoA ester accounting for the specific R-to S-inversion in vivo. [2][3][4][5][6][8][9][10][11] AMACR is highly conserved across species and the pathway is probably common in mammals and other species. Chemoprotective effects of 2-APAs have been previously reported, but their effects were ascribed to binding to p75 NTR or COX.…”

mentioning

confidence: 99%

Chiral inversion of 2-arylpropionyl-CoA esters by human α-methylacyl-CoA racemase 1A (P504S)—a potential mechanism for the anti-cancer effects of ibuprofen

et al. 2011

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(−)-R-fenoprofen: Formation of fenoprofenyl-coenzyme A by rat liver microsomes

Cited by 11 publications

References 12 publications

Detergents profoundly affect inhibitor potencies against both cyclo-oxygenase isoforms

Detergents profoundly affect inhibitor potencies against both cyclo-oxygenase isoforms

Unidirectional Inversion of Ibuprofen in Caco-2 Cells: Developing a Suitable Model for Presystemic Chiral Inversion Study

Chiral inversion of 2-arylpropionyl-CoA esters by human α-methylacyl-CoA racemase 1A (P504S)—a potential mechanism for the anti-cancer effects of ibuprofen

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