Home Metabolism Phospholipase (e.g. PLA) inhibitor - Lipoxygenase inhibitor U73122

U73122

Catalog No.S8011

For research use only.

U73122 is a potent phospholipase C (PLC) inhibitor, which reduces agonist-induced Ca2+ increases in platelets and PMN. U73122 potently inhibits human 5-lipoxygenase (5-LO).

U73122 Chemical Structure

CAS No. 112648-68-7

Selleck's U73122 has been cited by 49 publications

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Biological Activity

Description U73122 is a potent phospholipase C (PLC) inhibitor, which reduces agonist-induced Ca2+ increases in platelets and PMN. U73122 potently inhibits human 5-lipoxygenase (5-LO).
Targets
PLC [1]
In vitro

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. [1] 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. [2] 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. [3] 1 μM U73122 blocks bradykinin (BK)-induced increases in the intracellular free Ca2+ concentration in undifferentiated NG108-15 cell. The IC50 for a 20-min exposure is approximately 200 nM. 1 μM U73122 produces a small but significant increase in [Ca2+]i which results from Ca 2+ release from an intracellular store. In differentiated NG108-15 cells U73122 blocks completely depolarization-induced Ca2+ influx. In contrast, in DRG neurons U73122 inhibits only slightly voltage-sensitive Ca2+ channels. [4] U73122 is a relatively specific inhibitor of G-protein-mediated phospholipase C activation in pancreatic acini. U73122 inhibits phosphatidylinositol (PI) hydrolysis on stimulation with either cholecystokinin (by 81%) or carbachol (by 73%) at a maximal effect concentration of 10 μM. U73122 (10 μM) inhibits the increases in [Ca2+]i stimulated by high concentrations of secretagogues in fura-2-loaded acini. U73122 also inhibits the [Ca2+]i signal generated by directly stimulating G-proteins with sodium fluoride. U73122 rapidly inhibits the oscillating [Ca2+]i signal elicited by low concentrations of cholecystokinin or carbachol. [5] U73122 increases the activity of hPLCβ3 in a concentration-and time-dependent manner in a cell-free micellar system, with up to an 8-fold increase in enzyme activity and a EC50 of 13.6 μM. Activation of hPLCβ3 by U73122 requires covalent modification of cysteines. U73122 (10 μM) also activates hPLCγ1(>10-fold) and hPLCβ2(~2-fold); PLC δ1 is neither activated nor inhibited. [6]
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human Jurkat cells M2rFUGZ2dmO2aX;uJIF{e2G7 NUfrO5VCUW6qaXLpeIlwdiCxZjDoeY1idiC2ZXzvcYVz[XOnIHHjeIl3cXS7IHnuJIh2dWGwIFr1dotifCClZXzsd{BjgSCWUlHQJIF{e2G7LDDJR|UxRTBwMjFOwG0> NGnVSoU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC1N|U6Pid-MkSwOVM2QTZ:L3G+
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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. [3]

Protocol (from reference)

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
5% DMF+40% PEG300+5% Tween80+50% ddH2O
For best results, use promptly after mixing.

 1mg/ml

Chemical Information

Molecular Weight 464.64
Formula

C29H40N2O3
CAS No. 112648-68-7
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC12CCC3C(C1CCC2NCCCCCCN4C(=O)C=CC4=O)CCC5=C3C=CC(=C5)OC

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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