NSC-663284-DA-3003-1-DataSheet-生命科学试剂-MedChemExpressVIP

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemENSC663284Cat.No.:HY-100034CASNo.:383907-43-5Synonyms:DA-3003-1分⼦式:C₁₅H₁₆ClN₃O₃分⼦量:321.76作⽤靶点:Phosphatase;HistoneMethyltransferase作⽤通路:MetabolicEnzyme/Protease;Epigenetics储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥150mg/mL(466.19mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM3.1079mL15.5395mL31.0791mL5mM0.6216mL3.1079mL6.2158mL10mM0.3108mL1.5540mL3.1079mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(7.77mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.77mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.77mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性NSC663284(DA-3003-1)⼀种有效的，细胞可渗透的且不可逆的Cdc25dualspecificityphosphatase抑制剂，Cdc25B2的IC50为0.21μM。NSC663284表现出与Cdc25A，Cdc25B2和Cdc25C的混合竞争动⼒学，Ki值分别为29、95和89nM。NSC663284通过与SET结构域(Kdof370nM)的相互作⽤来抑制NSD2(IC50of170nM)酶的活性。IC50&TargetIC50:0.21μM(Cdc25B2)[1]体外研究NSC663284(3-100μM;48hours)hasameanIC50valueintheNCI60Cellhumantumorpanelof1.5±0.6μM,hasIC50valuesof0.2μMinhumanbreastcancerMDA-MB-435andMDA-Ncells,hasanIC50valueof1.7μMinhumanbreastMCF-7cellsinculture[1].NSC663284hasrelativeIC50valuesforCdc25B2(IC50=0.21μM)are20-and450-foldlowerthanforVHR(IC50=4.0μM)orPTP1B(IC50>4.0μM),respectively[1].体内研究NSC663284(intravenousinjection;2,3,and5mg/kg)inhibitsthegrowthofsubcutaneoushumancolonHT29xenograftsinSCIDmice.Afterasingledoseof5mg/kg,NSC663284isnotdetectableinplasmaortissuesbeyond5min.FollowingNSC663284treatmentoftumor-bearingSCIDmice,reducesglutathioneconcentrationsinHT29tumoraredecreasedtoagreaterextentandremaineddecreasedforlongerthanthereducedglutathioneconcentrationsinliverandkidneys[3].PROTOCOLAnimalMice:C.B.-17SCIDmicebearingHT29humancoloncarcinomaxenograftsarestratifiedintothefollowingAdministration[2]groupsof9-10animals:Control,vehiclecontrol,positivecontrol(gemcitabine,50mg/kg/dosei.v.),NSC663284atthefollowingdoses:2,3or5mg/kg/dosei.v..Themicearedosedevery4daysfor6doses,andbodyweightsandtumorvolumesarerecordedtwiceweekly.Tumorsaremeasuredwithcalipers,andtumorvolumesarecalculated.Micearefollowedfor3weeksfollowingthecompletionofthedosingtomonitortumorregrowth.Inasecondstudy,C.B.-17SCIDmicebearingMDA-MB-435humanbreastcancerxenograftsarestratifiedtothesametreatmentgroups,exceptthatpaclitaxelat20mg/kgi.v.every7daysisusedasthepositivecontrol[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•CommunBiol.2021Jul15;4(1):878.•MolCancerRes.2020Jan;18(1):91-104.•Bioengineered.2022May;13(5):13089-13107.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LazoJS,etal.DiscoveryandbiologicalevaluationofanewfamilyofpotentinhibitorsofthedualspecificityproteinphosphataseCdc25.JMedChem.2001Nov22;44(24):4042-9.[2].GuoJ,etal.PharmacologyandantitumoractivityofaquinolinedioneCdc25phosphataseinhibitorDA3003-1(NSC663284).AnticancerRes.2007Sep-Oct;27(5A):3067-73.[3].CoussensNP,etal.High-throughputscreeningwithnucleosomesubstrateidentifiessmall-moleculeinhibitorsofthehumanhistonelysinemethyltransferaseNSD2.JBiolChem.2018Aug31;293(35):13750-13765.Mc