Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemENSC663284Cat.No.:HY-100034CASNo.:383907-43-5Synonyms:DA-3003-1分?式:C??H??ClN?O?分?量:321.76作?靶點(diǎn):Phosphatase;HistoneMethyltransferase作?通路:MetabolicEnzyme/Protease;Epigenetics儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥150mg/mL(466.19mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.1079mL15.5395mL31.0791mL5mM0.6216mL3.1079mL6.2158mL10mM0.3108mL1.5540mL3.1079mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)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(qǐng)先按照InVitro?式配制澄的儲(chǔ)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(chǔ)備液可以根據(jù)儲(chǔ)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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(7.77mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.77mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.77mM);ClearsolutionBIOLOGICALACTIVITY?物活性NSC663284(DA-3003-1)?種有效的，細(xì)胞可滲透的且不可逆的Cdc25dualspecificityphosphatase抑制劑，Cdc25B2的IC50為0.21μM。NSC663284表現(xiàn)出與Cdc25A，Cdc25B2和Cdc25C的混合競(jìng)爭(zhēng)動(dòng)?學(xué)，Ki值分別為29、95和89nM。NSC663284通過與SET結(jié)構(gòu)域(Kdof370nM)的相互作?來抑制NSD2(IC50of170nM)酶的活性。IC50&TargetIC50:0.21μM(Cdc25B2)[1]體外研究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].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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