PS-1145-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPS-1145Cat.No.:HY-18008CASNo.:431898-65-6分?式:C??H??ClN?O分?量:322.75作?靶點:IKK;Apoptosis作?通路:NF-κB;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:20.83mg/mL(64.54mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.0984mL15.4919mL30.9837mL5mM0.6197mL3.0984mL6.1967mL10mM0.3098mL1.5492mL3.0984mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2.08mg/mL(6.44mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(6.44mM);ClearsolutionBIOLOGICALACTIVITY?物活性PS-1145?種IκB激酶(IKK)抑制劑，IC50為88nM。IC50&TargetIKK88nM(IC50)體外研究PS-1145blocksTNFα-inducedNF-κBactivationinadose-andtime-dependentfashioninMMcellsthroughinhibitionofIκBαphosphorylation.Dexamethasone(Dex),whichup-regulatesIκBαprotein,enhancesblockadeofNF-κBactivationbyPS-1145.PS-1145blockstheprotectiveeffectofIL-6againstDex-inducedapotosis.TNFα-inducedintracellularadhesionmolecule(ICAM)-1expressiononbothRPMI8226andMM.1ScellsisalsoinhibitedbyPS-1145.Moreover,PS-1145inhibitsbothIL-6secretionfrombonemarrowstromalcells(BMSCs)triggeredbyMMcelladhesionandproliferationofMMcellsadherenttoBMSCs[1].體內(nèi)研究AdministrationofeitherBortezomiborPS-1145(50mg/kg)resultsinasignificantdecreaseinserumlevelsofall3cytokinesthatisnonsignificantlydifferentfromthoseinmicethatunderwenttransplantationwithTCDBMalone[2].PS1145isinjectedintracerebroventricular(icv)asapretreatmenttoblockhypothalamicinflammationinducedbyIL-4inadultmaleWistarratsconsumingahigh-fatdiet(HFD)overan11-dayperiod.Thefourgroupsofratsaccordingtoicvpretreatment/treatmentconditionareVeh/Veh,Veh/IL-4,PS1145/Veh,andPS1145/IL-4.RatsintheVeh/IL-4groupdisplayincreasedweightgainontheHFDcomparedwiththeVeh/Vehgroup(P[3].PROTOCOLCellAssay[1]TheinhibitoryeffectofPS-1145onMMgrowthisassessedbymeasuringMTTdyeabsorbanceofthecells.MM.1Scellsareculturedfor48hwith0.2and1ng/mLTNFα,intheabsenceorpresenceof2.5μM,5μM,and10μMPS-1145.CellviabilityisassessedbyMTTassay.Cellsfrom48hculturesarepulsedwith10μLof5mg/mLMTTtoeachwellforthelast4hof48-hcultures,followedby100μLofisopropanolcontaining0.04NHCl.Absorbanceismeasuredat570nmusingaspectrophotometer[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration[2][3]C57BL/6(B6),B10.BR,andB6.SJLmiceareused.Micereceiveregularmousechowandacidifiedtapwateradlibitum.Bortezomibisadministeredintravenouslytoanimalsatadoseof1mg/kg,whereasPS-1145isgivenintraperitoneallyatadoseof50mg/kg.Thefirstdoseofeachagentisadministeredbeforeconditioningwithtotalbodyirradiation(TBI).Rats[3]Weight-matchedmaleWistarrats(320-350g)areused.Fourgroupsofrats(n=6/group)consumetheHFDfora9-daystudyperiod.Animalsineachgroupreceivetwoconsecutiveicvinjectionsthreetimes/wk.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEImmediatelypriortoicvinjectionofIL-4(100ng)orvehicle,allanimalsreceiveapretreatmenticvinjectionofeithertheIKKβinhibitorPS1145(10μg)oritsvehicle(saline).Foodintakeandbodyweightaremeasureddaily.Bodycompositionanalysisisconductedasaboveondays0and8.Onday9,animalsareeuthanizedandsamplescollected.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?ExpCellRes.2021Feb15;399(2):112468.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].HideshimaT,etal.NF-kappaBasatherapeutictargetinmultiplemyeloma.JBiolChem.2002May10;277(19):16639-47.[2].Vodanovic-JankovicS,etal.NF-kappaBasatargetforthepreventionofgraft-versus-hostdisease:comparativeefficacyofbortezomibandPS-1145.Blood.2006Jan15;107(2):827-34.[3].Oh-IS,etal.Centraladministrationofinterleukin-4exacerbateshypothalamicinflammationandweightgainduringhigh-fatfeeding.AmJPhysiolEndocrino