WNK463-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEWNK463Cat.No.:HY-100626CASNo.:2012607-27-9分?式:C??H??F?N?O?分?量:463.46作?靶點(diǎn):Ser/ThrProtease作?通路:MetabolicEnzyme/Protease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:≥30mg/mL(64.73mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.1577mL10.7884mL21.5768mL5mM0.4315mL2.1577mL4.3154mL10mM0.2158mL1.0788mL2.1577mL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；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。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。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(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，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(5.39mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.39mM);ClearsolutionBIOLOGICALACTIVITY?物活性WNK463?種?服的WNK激酶抑制劑，對(duì)于WNK1，WNK2，WNK3和WNK4的IC50值分別為5nM，1nM，6nM和9nM。IC50&TargetIC50:5nM(WNK1),1nM(WNK2),6nM(WNK3),and9nM(WNK4)[1]體外研究WNK463(50nM,1μΜ,10μΜ;6days;Humantissue-engineeredcorneas(hTECs))treatmentreducesphosphorylationoftheWNK1downstreamtargetsSPAK/OSR1inwoundedhTECs.WesternBlotAnalysis[2]CellLine:Humantissue-engineeredcorneas(hTECs)Concentration:50nM,1μΜ,10μΜIncubationTime:6daysResult:ReducedphosphorylationoftheWNK1downstreamtargetsSPAK/OSR1inwoundedhTECs.體內(nèi)研究WNK463(1-10mg/kg;oraladministration;4hours;SpontaneouslyhypertensiveSpragueDawleyrats)treatmentproducesdose-dependentdecreasesinbloodpressureandsimultaneousincreasesinheartrateinconsciousSHRs.WNK463producessignificantanddose-dependentincreasesinurineoutputaswellasurinarysodiumandpotassiumexcretionrates.WNK463isorallybioavailableinSpragueDawleyratswithahalf-lifeof2.1hours[1].AnimalModel:SpontaneouslyhypertensiveSpragueDawleyrats(34-42weeksofage)[1]Dosage:1mg/kg,3mg/kg,or10mg/kg(Pharmacokineticstudy)Administration:Oraladministration;4hoursResult:Decreasedinbloodpressureandsimultaneousincreasesinheartrate.WNK463producedsignificantanddose-dependentincreasedinurineoutputaswellasurinarysodiumandpotassiumexcretionrates.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NatCommun.2021Jul27;12(1):4546.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE?NatMetab.2019Jan;1(1):47-57.?Cancers.2020Mar2;12(3):575.?IntJMolSci.2022,23(20),12100.?UniversityCollegeLondon.FrancisCrickInstitute.2021Oct.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].YamadaKetal.Small-moleculeWNKinhibitionregulatescardiovascularandrenalfunction.NatChemBiol.2016Nov;12(11):896-898.[2].DesjardinsP,etal.ContributionoftheWNK1kinasetocornealwoundhealingusingthetissue-engineeredhumancorneaasaninvitromodel.JTissueEngRegenMed.2019Sep;13(9):1595-1608.McePdfHeightCaution:Producthasnotbeenfullyvali