SF2523-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESF2523Cat.No.:HY-101146CASNo.:1174428-47-7分⼦式:C₁₉H₁₇NO₅S分⼦量:371.41作⽤靶点:PI3K;EpigeneticReaderDomain;DNA-PK作⽤通路:PI3K/Akt/mTOR;Epigenetics;CellCycle/DNADamage储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥30mg/mL(80.77mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.6924mL13.4622mL26.9244mL5mM0.5385mL2.6924mL5.3849mL10mM0.2692mL1.3462mL2.6924mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(6.73mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.73mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性SF2523⼀种有效的选择性PI3K抑制剂，抑制PI3Kα，PI3Kγ，DNA-PK，BRD4和mTOR，IC50分别为34nM，158nM，9nM，241nM和280nM。IC50&TargetPI3KαPI3KγBRD4(BD1)DNA-PK34nM(IC50)158nM(IC50)241nM(IC50)9nM(IC50)mTOR280nM(IC50)体外研究SF2523treatmentdecreasesproteinlevelsofMYCNandCyclinD1,theMYCNtarget,andinhibitsAKTactivationbyblockingphosphorylationofAKTatSer473.SF2523treatmentleadstothedisplacementofBRD4frombothMYCNpromotersites.SF2523interactsrobustlywiththefull-lengthBRD4(Kd=140nM)andexhibitscomparableaffinitytotheBRD4firstBD(BD1)(Kd=150nM),howeveritbindsmoreweaklytothesecondBD(BD2)ofBRD4(Kd=710nM).ComparisonofbindingaffinitiesofSF2523forBDsofotherproteinsrevealthatitbindsequallywelltoBDsofBRD4,BRD2,andBRD3;showsmoderatebindingtoBDsofCECR2andBRDT;butassociatesmuchweakerwithotherBDs[2].体内研究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.户使⽤本产品发表的科研⽂献•SciRep.2022Apr12;12(1):6090.Seemorecustomervalidationsonwww.MedChemE2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师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