SF2523-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESF2523Cat.No.:HY-101146CASNo.:1174428-47-7分?式:C??H??NO?S分?量:371.41作?靶點:PI3K;EpigeneticReaderDomain;DNA-PK作?通路:PI3K/Akt/mTOR;Epigenetics;CellCycle/DNADamage儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥30mg/mL(80.77mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.6924mL13.4622mL26.9244mL5mM0.5385mL2.6924mL5.3849mL10mM0.2692mL1.3462mL2.6924mL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，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(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：(為保證實驗結(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)實驗的?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(6.73mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.73mM);ClearsolutionBIOLOGICALACTIVITY?物活性SF2523?種有效的選擇性PI3K抑制劑，抑制PI3Kα，PI3Kγ，DNA-PK，BRD4和mTOR，IC50分別為34nM，158nM，9nM，241nM和280nM。IC50&TargetPI3KαPI3KγBRD4(BD1)DNA-PK34nM(IC50)158nM(IC50)241nM(IC50)9nM(IC50)mTOR280nM(IC50)體外研究SF2523treatmentdecreasesproteinlevelsofMYCNandCyclinD1,theMYCNtarget,andinhibitsAKTactivationbyblockingphosphorylationofAKTatSer473.SF2523treatmentleadstothedisplacementofBRD4frombothMYCNpromotersites.SF2523interactsrobustlywiththefull-lengthBRD4(Kd=140nM)andexhibitscomparableaffinitytotheBRD4firstBD(BD1)(Kd=150nM),howeveritbindsmoreweaklytothesecondBD(BD2)ofBRD4(Kd=710nM).ComparisonofbindingaffinitiesofSF2523forBDsofotherproteinsrevealthatitbindsequallywelltoBDsofBRD4,BRD2,andBRD3;showsmoderatebindingtoBDsofCECR2andBRDT;butassociatesmuchweakerwithotherBDs[2].體內(nèi)研究SF2523treatmentresultsinasignificantreductionoftumorvolumecomparedwithcontrol.Importantly,SF2523showsnogrosstoxicitytothetreatedmice,asthereisnonotablechangeinbodyweight.TumorsfromSF2523-treatedmicehavemarkedlyreducedMYCN,pAKT,andCyclinD1levelscomparedwithlevelsoftheseproteinsinvehicle-treatedmicetumors[2].PROTOCOLAnimalMice:After20doftumorimplantation,micearetreatedwitheither(i)30mg/kgofSF2523formulatedin15%Administration[2]DMA+30%captisol,(ii)30mg/kgofJQ1formulatedin30%captisolincombinationwith30mg/kgofBKM120formulatedin15%ethanol+15%cremaphore,(iii)vehicle(15%ethanol+15%cremaphore,ascontrol),or(iv)anothervehicle(15%DMA+30%captisol,ascontrol)fivetimesaweek,untiltumorsareremovedonday35[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?SciRep.2022Apr12;12(1):6090.Seemorecustomervalidationsonwww.MedChemE2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEREFERENCES[1].CarlinoL,etal.DualKinase-BromodomainInhibitorsinAnticancerDrugDiscovery:AStructuralandPharmacologicalPerspective.JMedChem.2016Oct27;59(20):9305-9320.[2].AndrewsFH,etal.Dual-activityPI3K-BRD4inhibitorfortheorthogonalinhibitionofMYCtoblocktumorgrowthandmetastasis.ProcNatlAcadSciUSA.2017Feb14;114(7):E1072-E1080.McePdfHeightCaution:Producthasn