A Gαq-signaling-biased PAR1 antagonist
Q94 is a Gαq signaling-biased antagonist of proteinase-activated receptor 1 (PAR1; IC50 = 916 nM).1,2 It inhibits increases in intracellular calcium mobilization induced by thrombin or a PAR1-activating peptide, but not a PAR2-activating peptide, in HMEC-1 cells when used at concentrations of 1 and 10 μM.1 Q94 (5 mg/kg per day) decreases albuminuria in a mouse model of nephropathy induced by doxorubicin .3
1.Asteriti, S., Daniele, S., Porchia, F., et al.Modulation of PAR1 signalling by benzimidazole compoundsBr. J. Pharmacol.167(1)80-94(2012) 2.Deng, X., Mercer, P.F., Scotton, C.J., et al.Thrombin induces fibroblast CCL2/JE production and release via coupling of PAR1 to Gαq and cooperation between ERK1/2 and Rho kinase signaling pathwaysMol. Biol. Cell19(6)2520-2533(2008) 3.Guan, Y., Nakano, D., Zhang, Y., et al.A protease-activated receptor-1 antagonist protects against podocyte injury in a mouse model of nephropathyJ. Pharmacol. Sci.135(2)81-88(2017)
动态评分
0.0