Cytosolic phospholipase A2α (cPLA2α) specifically catalyzes the hydrolysis of arachidonic acid from the sn-2-ester position of membrane phospholipids, playing a central role in initiating the synthesis of prostaglandins and leukotrienes, both important mediators of the inflammatory process.1 CAY10641 is an inactive alcohol derivative of a highly potent (IC50 = 12 nM) cPLA2α inhibitor. 2 The parent compound demonstrates strong anti-inflammatory effects when applied topically at a dose of 0.1 mg/ear in a mouse model of acute irritant contact dermatitis.2 CAY10641 is rapidly cleared from the blood stream (only 0.5 μg/ml remains 30 minutes after 10 mg/kg intravenous administration to mice).2 However, no other biological effects have been reported.
1.Schaloske, R.H., and Dennis, E.A.The phospholipase A2 superfamily and its group numbering systemBiochemica et Biophysica Acta17611246-1259(2006)
2.Drews, A., Bovens, S., Roebrock, K., et al.1-(5-carboxyindol-1-yl)propan-2-one inhibitors of human cytosolic phospholipase A2α with reduced lipophilicity: Synthesis, biological activity, metabolic stability, solubility, bioavailability, and topical in vivo activityJournal of Medicinal Chemistry535165-5178(2010)
