W-7-hydrochloride-DataSheet-生命科學(xué)試劑-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEW-7hydrochlorideCat.No.:HY-100912CASNo.:61714-27-0分?式:C??H??Cl?N?O?S分?量:377.33作?靶點(diǎn):CaMK;Phosphodiesterase(PDE);Myosin;Apoptosis作?通路:NeuronalSignaling;MetabolicEnzyme/Protease;Cytoskeleton;Apoptosis儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:250mg/mL(662.55mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.6502mL13.2510mL26.5020mL5mM0.5300mL2.6502mL5.3004mL10mM0.2650mL1.3251mL2.6502mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案，配制前請(qǐng)先配制澄的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分?指該溶劑在您配制終溶液中的體積占?)：1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(5.51mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(5.51mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoil1/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(5.51mM);ClearsolutionBIOLOGICALACTIVITY?物活性W-7hydrochloride?種選擇性的鈣調(diào)蛋?(calmodulin)拮抗劑。W-7hydrochloride抑制Ca2+-鈣調(diào)蛋?依賴性磷酸?酯酶(phosphodiesterase)和肌球蛋?輕鏈激酶(myosinlightchainkinase)，IC50值分別為28μM和51μM。W-7hydrochloride可誘導(dǎo)細(xì)胞凋亡(apoptosis)，并具有抗癌活性。IC50&TargetIC50:28μM(Phosphodiesterase)and51μM(Myosinlightchainkinase)[1]體外研究W-7isdistributedmainlyinthecytoplasm,andinhibitsproliferationofChinesehamsterovaryK1(CHO-K1)cells.W-7selectivelyblocksthephaseofthecellcycle(G1/Sboundaryphase)inamanner.25μMW-7arreststhegrowthofthecellsattheG1/Sboundaryphaseofthecellcycle[1].W-7(100μM)exhibitsasimilarextentofantagonismbetweenthecontractileresponsestocarbacholandKCl.Theincreaseinmyosinlightchain(P-LC)phosphatecontentinresponseto1-minstimulationwith10μMcarbacholisinhibitedbyW-7.W-7antagonizesthesmoothmusclecontractionthroughtheinhibitionoftheinitialincreaseintheP-LCphosphorylation[2].TreatmentwithW-7resultsinthedose-dependentinhibitionofcellproliferationinvarioushumanmultiplemyelomacelllines.W-7inducesG1phasecellcyclearrestbydownregulatingcyclinsandupregulatingp21cip1.W-7inducesapoptosisviacaspaseactivation;thisoccurredpartlythroughtheelevationofintracellularcalciumlevelsandmitochondrialmembranepotentialdepolarizationandthroughinhibitionoftheSTAT3phosphorylationandsubsequentdownregulationofMcl-1protein[3].W-7competitivelyinhibitsCa2+/calmodulin-dependentphosphodiesterasewithaKivalueof300μM[4].體內(nèi)研究W-7(3mg/kg;intraperitonealinjection;on5consecutivedaysperweek;femaleBALB/cnumice)treatmentsignificantlyreducestumorgrowthinamurineMMmodel[3].AnimalModel:FemaleBALB/cnumice(6-week-old)injectedwithRPMI8226cells[3]Dosage:3mg/kgAdministration:Intraperitonealinjection;on5consecutivedaysperweekResult:SignificantlyreducedtumorgrowthinamurineMMmodel.REFERENCES[1].HHidaka,etal.N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide,aCalmodulinAntagonist,InhibitsCellProliferation.ProcNatlAcadSciUSA.1981Jul;78(7):4354-7.[2].MAsano.DivergentPharmacologicalEffectsofThreeCalmodulinAntagonists,N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide(W-7),ChlorpromazineandCalmidazolium,onIsometricTensionDevelopmentandMyosinLightChainPhosphorylationinIntactBovineTrachealSmoothMuscle.JPharmacolExpTher.1989Nov;251(2):764-73.[3].HItoh,etal.DirectInteractionofCalmodulinAntagonistsWithCa2+/calmodulin-dependentCyclicNucleotidePhosphodiesterase.J2/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemEBiochem.1984Dec;96(6):1721-6.[4].ShigeyukiYokokura,etal.CalmodulinAntagonistsInduceCellCycleArrestandApoptosisinVitroandInhibitTumorGrowthinVivoinHumanMultipleMyeloma.BMCCancer.2014Nov26;14:882.McePdf