S-Crizotinib-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemE(S)-CrizotinibCat.No.:HY-100549CASNo.:1374356-45-2分?式:C??H??Cl?FN?O分?量:450.34作?靶點:DNA/RNASynthesis;Apoptosis作?通路:CellCycle/DNADamage;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:12.5mg/mL(27.76mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.2205mL11.1027mL22.2054mL5mM0.4441mL2.2205mL4.4411mL10mM0.2221mL1.1103mL2.2205mL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?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據(jù)您的實驗動物和給藥?式選擇適當?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：(為保證實驗結果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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%salineSolubility:≥1.25mg/mL(2.78mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1.25mg/mL(2.78mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.25mg/mL(2.78mM);ClearsolutionBIOLOGICALACTIVITY?物活性(S)-Crizotinib?種有效的選擇性MTH1(mutT同物)抑制劑，IC50為330nM。(S)-Crizotinib通過抑制MTH1破壞核苷酸庫的穩(wěn)態(tài)，誘導DNA單鏈斷裂的增加，激活?結腸癌細胞的DNA修復，并有效抑制動物模型中的腫瘤?長。IC50&TargetIC50:330nM(MTH1)[1]體外研究(S)-crizotinib(0.625-80μM;24hours)decreasestheviabilityofNCI-H460,H1975andA549cellswithIC50valuesof14.29,16.54and11.25μM,respectively[2].(S)-crizotinib(10-30μM;24hours)inducesNCI-H460,H1975andA549cellsapoptosis[2].(S)-crizotinib(10-30μM;24hours)decreasesBcl-2:Baxratio.(S)-crizotinibdecreasesBcelllymphoma2(Bcl-2),andBcl-2associatedproteinx(Bax)iseitherunaltered(H460cells)orshowsanincrease(H1975cells)[2].(S)-Crizotinibinducesapoptosisinhumannon-smallcelllungcancer(NSCLC)cellsbyactivatingROS-dependentERstressapoptoticpathwayindependentofmutThomologue(MTH1)[2].CellViabilityAssay[2]CellLine:NSCLCcells,NCI-H460,H1975andA549cellsConcentration:0.625,1.25,2.5,5,10,20,40,60,80μMIncubationTime:24hoursResult:DecreasedtheviabilityofNCI-H460,H1975andA549cellswithIC50valuesof14.29,16.54and11.25μM,respectively.ApoptosisAnalysis[2]CellLine:NSCLCcells,NCI-H460,H1975andA549cellsConcentration:10,20or30μMIncubationTime:24hoursResult:Inducedcellsapoptosis.WesternBlotAnalysis[2]CellLine:NSCLCcells,NCI-H460,H1975andA549cells2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEConcentration:10,20or30μMIncubationTime:24hoursResult:DecreasedBcl-2:Baxratio.體內研究(S)-crizotinib(7.5or15mg/kg;intraperitonealinjections;oncedailyfor10days)resultsinsignificantreductionsinbothtumorvolumeandtumorweight[2].AnimalModel:Five-week-old,athymicBALB/cnu/nufemalemice(17-19g)withNCI-H460cells[2]Dosage:7.5or15mg/kgAdministration:Intraperitonealinjections;oncedailyfor10daysResult:Resultedinsignificantreductionsinbothtumorvolumeandtumorweight.REFERENCES[1].HuberKV,etal.StereospecifictargetingofMTH1by(S)-crizotinibasananticancerstrategy.Nature.2014Apr10;508(7495):222-7.[2].DaiX,etal.(S)-crizotinibinducesapoptosisinhumannon-smallcelllungcancercellsbyactivatingROSindependentofMTH1.JExpClinCancerRes.2017Sep7;36(1):120.McePdfHeightCaution:Producthasnot