A cyclic depsipeptide Gαq/11 inhibitor
YM-254890 is cyclic depsipeptide originally isolated from Chromobacterium and an inhibitor of Gαq/11.[1] It inhibits Gαq/11-mediated intracellular calcium mobilization induced by 2MeSADP or methacholine in C6-15 cells expressing the purinergic P2Y1 receptor (IC50 = 0.15 μM) and in CHO cells expressing M1 muscarinic acetylcholine receptors (IC50 = 0.15 μM), respectively, but has no effect on Gαi-mediated calcium mobilization induced by fMLP in HL-60 cells (IC50 = >10 μM). YM-254890 inhibits platelet aggregation induced by ADP, collagen, thrombin receptor agonist peptide (TRAP), arachidonic acid , or U-46619 in isolated human platelet-rich plasma (IC50s = 0.39, 0.15, 0.71, 0.25, and 0.34 μM, respectively).[2] It reduces shear stress-induced thrombus formation in isolated human whole blood. YM-254890 (1, 3, and 10 μg/kg) reduces platelet thrombus formation in a cynomolgus monkey model of femoral artery thrombosis.
Reference:
[1]. Takasaki, J., Saito, T., Taniguchi, M., et al. A Novel Gɑq/11-selective Inhibitor. J. Biol. Chem. 279(46), 47438-47445 (2004).
[2]. Uemura, T., Kawasaki, T., Taniguchi, M., et al. Biological properties of a specific Gɑq/11 inhibitor, YM-254890, on platelet functions and thrombus formation under high-shear stress. Br. J. Pharmacol. 148(1), 61-69 (2006).
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