T025-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemET025Cat.No.:HY-112296CASNo.:2407433-00-3分?式:C??H??N?分?量:382.42作?靶點(diǎn):CDK;Apoptosis;DYRK作?通路:CellCycle/DNADamage;Apoptosis;ProteinTyrosineKinase/RTK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:8.25mg/mL(21.57mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.6149mL13.0746mL26.1493mL5mM0.5230mL2.6149mL5.2299mL10mM0.2615mL1.3075mL2.6149mL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?。BIOLOGICALACTIVITY?物活性T025?服有效的Cdc2-like激酶(CLK)抑制劑，對CLK1，CLK2，CLK3，CLK4，DYRK1A，DYRK1B和DYRK2的Kd分別為4.8，0.096，6.5，0.61，0.074，1.5和32nM。T025誘導(dǎo)caspase-3/7介導(dǎo)的細(xì)胞凋亡(apoptosis)。T025可降低CLK依賴性磷酸化。T025在?液和實(shí)體癌細(xì)胞系中均具有抗增殖活性(IC50值：30-300nM)。T025具有抗腫瘤功效，主?于MYC驅(qū)動(dòng)的疾病研究。1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIC50&TargetCLK2CLK4CLK1CLK30.096nM(Kd)0.61nM(Kd)4.8nM(Kd)6.5nM(Kd)DYRK1ADYRK1BDYRK20.074nM(Kd)1.5nM(Kd)32nM(Kd)體外研究T025(0-1000nM;72hours)significantlysuppressesthegrowthofMDA-MB-468cellsinadose-dependentmanner[1].T025(0-1000nM;6hours)reducesphosphorylationlevelsinMDA-MB-468cells[1].CellViabilityAssay[1]CellLine:MDA-MB-468cellsConcentration:1,10,100and1000nMIncubationTime:72hoursResult:Resultedinconcentrationdependentgrowthinhibition.WesternBlotAnalysis[1]CellLine:MDA-MB-468cellsConcentration:0,10,30,100,300and1000nMIncubationTime:6hoursResult:DecreasedbothpCLK2andCLK2.體內(nèi)研究T025(50mg/kg;p.o.;2,4,8hours,Balb/cnudemice(7to8week-oldfemales).)suppresstheCLK-dependentphosphorylationandinduceskippingexoninvariousgenes[1].T025(50mg/kg;p.o.;twicedailyon2daysperweek,for3weeks,Balb/cnudemice(7to8week-oldfemales).)inhibitsMDA-MB-468xenograftmicetumorgrowthandwithoutaffectbodyweight[1].AnimalModel:Balb/cnudemice(7to8week-oldfemales)[1]Dosage:50mg/kgAdministration:Oraladministration;2,4,8hours.Result:pCLK2detectedwithimmunohistochemistryandimmunoblottingdecreased,byareductionintheRPS6KB1exon7andBCLAF1exon11percentagesplice-in(PSI)values.AnimalModel:Balb/cnudemice(7to8week-oldfemales)[1]2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEDosage:50mg/kgAdministration:Oraladministration;twicedailyon2daysperweek,for3weeks.Result:Suppressedtumorgrowthand<10%nadirbodyweightloss.REFERENCES[1].IwaiK,etal.Anti-tumorefficacyofanovelCLKinhibitorviatargetingRNAsplicingandMYC-dependentvulnerability.EMBOMolMed.2018Jun;10(6):e8289.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalap