Characterization of CGS 8515 as a selective 5-lipoxygenase (5-LO) inhibitor.

Abstract

1. CGS 8515 selectively inhibited 5-LO (IC50 = 0.1 microM) with negligible effect on CO, 12-LO, 15-LO and TxS at concentrations up to 100 microM. 2. CGS 8515 selectively inhibited A23187-induced formation of 5-LO products in rat and human whole blood with a 20-70 fold separation of effects over the formation of CO products. 3. Ex vivo and in vivo studies with rats showed that CGS 8515, at an oral dose of 2-50 mg/kg, significantly inhibited A23187-induced formation of LTs in whole blood and in the lung. The effect persisted for at least 6 h in the ex vivo blood model. 4. CGS 8515, at oral doses as low as 5 mg/kg, significantly suppressed exudate volume and leukocyte migration in the carrageenan-induced pleurisy and sponge models in the rat.

• Authors: E C Ku, A Raychaudhuri, G Ghai, E F Kimble, W H Lee, C Colombo, R Dotson, D White, T D Oglesby, J W Wasley
• Journal: Advances in prostaglandin, thromboxane, and leukotriene research (Adv Prostaglandin Thromboxane Leukot Res) Vol. 19 Pg. 86-9 ( 1989) ISSN: 0732-8141 [Print] United States
• PMID: 2526568 (Publication Type: Journal Article)

Chemical References

• Arachidonic Acids
• Lipoxygenase Inhibitors
• Naphthoquinones
• ortho-Aminobenzoates
• methyl 2-((3,4-dihydro-3,4-dioxo-1-naphthalenyl)amino)benzoate
• Calcimycin
• Arachidonate Lipoxygenases
• Arachidonate 5-Lipoxygenase

Topics

• Animals
• Arachidonate 5-Lipoxygenase (blood)
• Arachidonate Lipoxygenases (blood)
• Arachidonic Acids (blood)
• Calcimycin (pharmacology)
• Cell Movement
• Humans
• Kinetics
• Leukocytes (drug effects, enzymology, physiology)
• Lipoxygenase Inhibitors
• Naphthoquinones (pharmacology)
• Rats
• ortho-Aminobenzoates (pharmacology)