受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C29H40N2O3 |
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分子量 | 464.64 | CAS No. | 112648-68-7 | ||||
Solubility (25°C)* | 体外 | DMF (warmed with 50ºC water bath) | 24 mg/mL (51.65 mM) | ||||
DMSO (warmed with 50ºC water bath) | 0.01 mg/mL (0.02 mM) | ||||||
Water | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | 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). |
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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] |
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] |
キナーゼアッセイ | Phosphoinositide-specific phospholipase C activity assay | |
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Assay mixtures (0.2 mL) contains assay buffer (without leupeptin), CaCl2 (an amount calculated to produce a Ca-EGTA buffer with the required free Ca2+ concentration), platelet soluble fraction (5-15 μg of protein) and 4 nmol of either phosphatidyl[3H]inositol or phosphatidyl[3H]inositol 4,5-bisphosphate. Substrata mixtures consists of either phosphatidyl[3H]inositol (3.4 Ci/mol) plus 1-pahnitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (1:0.4 M ratio) or phosphatidyl[3H]inositol4,5-bisphosphate (7 Ci/mol) plus 1-palmitoyl 2-oleoyl-sn-giycero-3-phosphoethanolamine (1:4 M ratio). Substrate mixtures are prepared as l0× suspensions of small unilamellar vesicles by consonication of the lipids in assay buffer (Vibra Cell microprobe sonicator, 75 W, 2 times 60 sec). U-73122 is added to assay mixtures in 2 μL of DMSO. This amount of DMSO has a negligible effect on phospholipase C activity under these conditions. Assay mixtures are incubated in glass tubes at 37 ℃ for 10 min and then quenched with 1.6 mL of chloroform/rnethanol/HC1 (1 N) (108:108:25, by vol). After vigorous mixing and centrifugation (500 g for 10 min), a portion (0.7 mL) of the aqueous upper layer (0.9 mL) is transferred to a scintillation vial that contains 10 mL of ACS scintillation fluid. Tritium in water-soluble products (>90% being inositol phosphates) is measured by liquid scintillation spectrornetry. Phosphoinositide hydrolysis under these conditions never exceeds 10% of total added and proceeded at a constant rate throughout the incubation period. Blank values are determined from assay mixtures in which platelet soluble fraction is added after the stopping reagent. | ||
細胞アッセイ | 細胞株 | Cell-free assays |
濃度 | 6 µM | |
反応時間 | ||
実験の流れ | ||
動物実験 | 動物モデル | Swiss-Webster mic |
投薬量 | 30 mg/kg | |
投与方法 | i.p. |
, , Cell Res, 2017, 27(6):748-763
, , Virus Genes, 2016, 53(2):179-189
Data from [Data independently produced by , , J Neurosci, 2016, 36(16):4534-48.]
Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src [ Nat Commun, 2024, 15(1):1300] | PubMed: 38346942 |
Bactericidal/permeability-increasing protein instructs dendritic cells to elicit Th22 cell response [ Cell Rep, 2024, 43(3):113929] | PubMed: 38457343 |
Microbial metabolite butyrate promotes anti-PD-1 antitumor efficacy by modulating T cell receptor signaling of cytotoxic CD8 T cell [ Gut Microbes, 2023, 15(2):2249143] | PubMed: 37635362 |
Microbial metabolite butyrate promotes anti-PD-1 antitumor efficacy by modulating T cell receptor signaling of cytotoxic CD8 T cell [ Gut Microbes, 2023, 15(2):2249143] | PubMed: 37635362 |
Inhibiting the glycerophosphodiesterase EDI3 in ER-HER2+ breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth [ J Exp Clin Cancer Res, 2023, 42(1):25] | PubMed: 36670508 |
PDE4DIP contributes to colorectal cancer growth and chemoresistance through modulation of the NF1/RAS signaling axis [ Cell Death Dis, 2023, 14(6):373] | PubMed: 37355626 |
PDE4DIP contributes to colorectal cancer growth and chemoresistance through modulation of the NF1/RAS signaling axis [ Cell Death Dis, 2023, 14(6):373] | PubMed: 37355626 |
A covalently linked probe to monitor local membrane properties surrounding plasma membrane proteins [ J Cell Biol, 2023, 222(3)e202206119] | PubMed: 36571579 |
Opsin 3 mediates UVA-induced keratinocyte supranuclear melanin cap formation [ Commun Biol, 2023, 6(1):238] | PubMed: 36869204 |
Phospholipid metabolic adaptation promotes survival of IDH2 mutant acute myeloid leukemia cells [ Cancer Sci, 2023, 10.1111/cas.15994] | PubMed: 37882467 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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