GSK503-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGSK503Cat.No.:HY-12856CASNo.:1346572-63-1分?式:C??H??N?O?分?量:526.67作?靶點(diǎn):HistoneMethyltransferase作?通路:Epigenetics儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥44mg/mL(83.54mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.8987mL9.4936mL18.9872mL5mM0.3797mL1.8987mL3.7974mL10mM0.1899mL0.9494mL1.8987mL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(fù)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(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(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?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，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%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(4.75mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.75mM);ClearsolutionBIOLOGICALACTIVITY?物活性GSK503?效特異性的EZH2甲轉(zhuǎn)移酶抑制劑，Kiapp值為3到27nM。IC50&TargetEZH2體外研究GSK503inhibitsthemethyltransferaseactivityofwildtypeandmutantEZH2withsimilarpotency(Kiapp=3-27nM)andisstructurallyrelatedtoGSK126andGSK343.GSK503is>200foldselectiveoverEZH1(Kiapp=636nM)and>4000foldselectiveoverotherhistonemethyltransferases[1].體內(nèi)研究Inamelanomamousemodel,conditionalEZH2ablationasmuchastreatmentwiththeGSK503stabilizesthediseasethroughinhibitionofgrowthandvirtuallyabolishesmetastasesformationwithoutaffectingnormalmelanocytebiology[2].GSK503displaysfavorablepharmacokineticsinmice.GSK503,butnotvehicle,preventstheformationofgerminalcenterafterSRBCorNP-KLHimmunization,phenocopyingtheEzh2nullphenotype.GSK503treatmentleadstoreducednumbersofGCB-cellsbyflowcytometry,reducesnumberandvolumeofGCsbyimmunohistochemistry,andimpairsformationhighaffinityantibodies[1].PROTOCOLAnimalMice:TopharmacologicallyinhibitEzh2activity,Tyr::N-RasQ61KInk4a-/-andC57Bl/6micearesubjectedtoAdministration[2]treatmentwithGSK503,whichisdiluted(15mg/mL)in20%Captisolsolution.EfficientEzh2inhibitionisachievedbydailyintraperitonealinjectionsof150mg/kgGSK503over35consecutivedays.MicearemonitoredduringandaftertreatmenttomeasureGSK503-inducedreversibleweightloss.C57Bl/6andFoxn1nu/numiceengraftedwithmelanomacellsaresubjectedtoTMandGSK503treatmentasdescribedabove[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?ProcNatlAcadSciUSA.2019Feb19;116(8):2961-2966.?PLoSPathog.2020Mar24;16(3):e1008429.?Patent.US20180263995A1.?Oncotarget.2017Apr25;8(35):58654-58667.Seemorecustomervalidationsonwww.MedChemEREFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].BéguelinW,etal.EZH2isrequiredforgerminalcenterformationandsomaticEZH2mutationspromotelymphoidtransformation.CancerCell.2013May13;23(5):677-92.[2].ZinggD,etal.TheepigeneticmodifierEZH2controlsmelanomagrowthandmetastasisthroughsilencingofdistincttumoursuppressors.NatCommun.2015Jan22;6:6051.McePdfHeightCaution:Producthasnotbeen