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- W2024494656 abstract "In this study we report the in vitro inhibition of leukotriene synthesis in calcium ionophore (A23187)-stimulated, intact human blood neutrophils by AHR-5333. The results showed that AHR-5333 inhibits 5-HETE, LTB 4 and LTC 4 synthesis with IC 50 values of 13.9, 13.7 and 6.9 μM, respectively. Further examination of the effect of AHR-5333 on individual reaction of the 5-lipoxygenase pathway (i.e. conversion of LTA 4 , to LTB 4 , LTA 4 to LTC 4 , and arachidonic acid to 5-HETE) showed that this agent was not inhibitory to LTA 4 expoxyhydrolase and glutathione-S-transferase activity in neutrophil homogenates. However, conversion of arachidonic acid (30 μM) to 5-HETE was half maximally inhibited by 20 μM AHR-5333 in the cell-free system. The inhibition of LTB 4 and LTC 4 formation in intact neutrophils by AHR-5333 appears to be entirely due to a selective inhibition of 5-lipoxygenase activity and an impaired formation of LTA 4 , which serves as substrate for LTA 4 epoxyhydrolase and glutathione-S-transferase. AHR-5333 did not affect the transformationof exogenous arachidonic acid to thromboxane B 2 , HHT and 12-HETE in preparations of washed human platelets, indicating that this agent has no effect on platelet prostaglandin H synthase, thromboxane synthase and 12-lipoxygenase activity. The lack of inhibitory activity of AHR-5333 on prostaglandin H synthase activity was confirmed with microsomal preparation of sheep vesicular glands." @default.
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- W2024494656 date "1989-10-01" @default.
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- W2024494656 title "1-[4-[3-[4-[Bis (4-fluorophenyl) hydroxymethyl]-1-piperidinyl] propoxy]-3]-methoxyphenyl] ethanone (AHR-5333): A selective human blood neutrophil 5-lipoxygenase inhibitor" @default.
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- W2024494656 doi "https://doi.org/10.1016/0090-6980(89)90130-5" @default.
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