A PLA2 inhibitor
ONO-RS-082 is a reversible inhibitor of Ca2+-independent phospholipase A2.
Phospholipases A2 (PLA2s) are enzymes releasing fatty acids from the second carbon group of glycerol. This particular phospholipase can specifically recognize the sn-2 acyl bond of phospholipids and can catalytically hydrolyze the bond releasing arachidonic acid and lysophosphatidic acid..
In vitro: Previous study found that human platelets stimulated by epinephrine led to enhanced turnover of phosphatidylinositol 4,5-bisphosphate, accumulated inositol trisphosphate, diacylglycerol, and phosphatidic acid, indicating stimulation of phospholipase C. It was shown that these responses could be completely blocked by inhibitors of alpha 2-adrenergic receptors including ONO-RS-082 or removal of fibrinogen. In addition, epinephrine could evoked an increased turnover of ester-linked arachidonic acid in aspirin treated platelets that was inhibited by ONO-RS-082 or the absence of fibrinogen. Moreover, it was found that ONO-RS-082 at 3.5 μM was able to inhibit epinephrine-stimulated thromboxane production in human platelets. ONO-RS-082 could also disrupt endosome tubule formation and maintenance of the Golgi complex [1].
In vivo: Up to now, there is no animal in vivo data reported.
Clinical trial: So far, no clinical study has been conducted.
Reference:
[1] Banga, H.?S.,Simons, E.R.,Brass, L.F., et al. Activation of phospholipases A and C in human platelets exposed to epinephrine: Role of glycoproteins IIb/IIIa and dual role of epinephrine. Proc. Natl. Acad. Sci. USA 83(23), 9197-9201 (1986).
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