U-73122 is a potent phospholipase C (PLC) inhibitor with IC50 value of ~6 μM [1].?
PLC is a class of membrane-associated enzymes that catalyzes the hydrolysis of a membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2), to produce two intracellular messengers, diacylglycerol and inositol-triphosphate, which, in turn, mediate the activation of protein kinase C (PKC) and intracellular Ca2+ release, respectively. It plays an important role in various signal transduction pathways [1].?
U-73122 significantly inhibited recombinant human PLC-β2 with IC50 value of ~6 μM, while showing little effect on PLC-β1, PLC-β3 or PLC-β4. In human neutrophils, U-73122 reduced interleukin-8 and leukotriene B4-induced Ca2+ flux and chemotaxis with IC50 values of ~6 μM and ~5 μM, respectively [1].?
In rats, U-73122 (30 mg/kg, i.p.) inhibited hind paw swelling by 65% and 80% at 1 h and 3 h post-carrageenan challenge. Moreover, pretreatment of U-73122 (1 mg/kg, 3 mg/kg and 10 mg/kg, respectively, i.v.) effectively suppressed TPA-induced mouse ear edema in a dose-dependent manner [1].?
Reference:
[1]. Hou C, Kirchner T, Singer M, et al. In vivo activity of a phospholipase C inhibitor, 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), in acute and chronic inflammatory reactions. Journal of Pharmacology and Experimental Therapeutics, 2004, 309(2): 697-704.
