product name U73122
Description: U73122 is a novel and potent phospholipase C (PLC) inhibitor, which reduces agonist-induced Ca2+ increases in platelets and PMN. U-73122 is widely used as a tool to investigate the involvement of the phosphoinositide-specific phospholipase C (PLC) in signal transduction, particularly in studies attempting to characterize pathways leading to intracellular Ca2+ mobilization upon agonist challenge. U-73122 directly blocks PLC isoenzymes in vivo and in vitro.
References: J Pharmacol Exp Ther. 1990 Nov;255(2):756-68; J Pharmacol Exp Ther. 2004 May;309(2):697-704.
464.64
Formula
C29H40N2O3
CAS No.
112648-68-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 0.01 mg/mL warmed (0.02 mM)
Water: <1 mg/mL
Ethanol:
Solubility (In vivo)
2% Tween 80+saline: 5mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: U73122 significantly inhibits aggregation of human platelets induced by a variety of agonists, including collagen, thrombin, ADP, arachidonic acid, with IC50 of 1-5 μM. U-73122 (10 μM) inhibits the production of IP3 and the subsequent rapid increase in cytosolic Ca2+ induced by either thrombin or U-46619 through inhibiting hydrolysis of phosphatidyl[3H]inositol and phosphatldyl[3H]inosito1 4,5-bisphosphate catalyzed by a soluble fraction from platelets (Ki=9 and 40 μM, respectively). U-73122 inhibits thromboxane B production induced by collagen through inhibiting receptor-coupled mobilization of arachidonic acid. U73122 inhibits also FMLP-induced aggregation of human polymorphonuclear neutrophils and the associated production of IP3 and diacylglycerol. U-73122 causes a concentration-dependent inhibition of C5a, FMLP, PAF and LTB4-induced MPO and B12-BP release from cyto-chalasin B-treated PMNs. The IC50 values are 60 (FMLP), 110 (LTB4), 115 (C5a) and 120 (PAF) nM for MPO release; and 105 (FMLP), 110 (LTB4), 120 (C5a) and 140 (PAY) nM for B12-BP release. U-73122 is also a potent inhibitor of superoxide anion production by cytochalasin B-treated PMNs activated with either C5a or FMLP with IC50 of 160 and 300 nM, respectively. U-73122 causes suppression of the rise in [Ca2+]i, IP3 production and DAG production in FMLP-stimulated PMNs with IC50 of 500 nM, 2 μM, and 2 μM, respectively. 3 μM U-73122 causes 100% inhibition of FMLP-induced GTPase activity. U-73122 causes a concentration-dependent inhibition of the FMLP-evoked association of PKC with the extractable particulate fraction of PMNs, but not a soluble preparation of PMN PKC. U73122 significantly inhibits recombinant human PLC-β2, with an IC50 of ~6 μM. U73122 has little effect on PLC-β1, PLC-β3, or PLC-β4. U73122 reduces interleukin-8 and leukotriene B4-induced Ca2+ flux and chemotaxis in human neutrophils with IC50 of ~6 μM and ~5 μM, respectively. Kinase Assay: Cell Assay: |
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| In Vivo | U73122 (30 mg/kg i.p.) blocks swelling of rats hind paw by 65 and 80% at 1 and 3 h postcarrageenan challenge. U73122 (0.1 mg/mL) inhibits carrageenan-induced macrophage and lymphocyte accumulation into subcutaneous chambers in dogs by 65 and 74%, respectively. U73122 (30 mg/kg i.p.) totally inhibits the LPS-induced increase in macrophage and lymphocyte infiltration and prostaglandin E2 production (by 80%) in a mouse peritonitis model, and inhibits and 12- O-tetradecanoyl-phorbol-13-acetate-induced ear edema in mice. |
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| Formulation & Dosage | |
| References | J Pharmacol Exp Ther. 1990 Nov;255(2):756-68; J Pharmacol Exp Ther. 2004 May;309(2):697-704. |
