Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemESCR7pyrazineCat.No.:HY-107845CASNo.:14892-97-8分?式:C??H??N?OS分?量:332.38作?靶點:CRISPR/Cas9;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:100mg/mL(300.86mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.0086mL15.0430mL30.0860mL5mM0.6017mL3.0086mL6.0172mL10mM0.3009mL1.5043mL3.0086mL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，并請注意儲備液的保存?式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案，配制前請先配制澄的儲備液，再依次添加助溶劑(為保證實驗結(jié)果的可靠性，體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分?指該溶劑在您配制終溶液中的體積占?)：1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(7.52mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.52mM);ClearsolutionBIOLOGICALACTIVITY1/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemE?物活性SCR7pyrazine?種DNA連接酶IV(DNAligaseIV)抑制劑，它以連接酶IV依賴的?式阻斷?同末端連接(NHEJ)。SCR7pyrazine也?種CRISPR/Cas9的增強(qiáng)?，可提?Cas9介導(dǎo)的同性定向修復(fù)(HDR)的效率。SCR7pyrazine誘導(dǎo)細(xì)胞凋亡(apoptosis)并具有抗癌活性。IC50&TargetDNALigaseIV[1]CRISPR/Cas9[2]體外研究SCR7pyrazine(20-100μM;24hours;MCF7cells)treatmentinterfereswithNHEJincells,leadingtoaccumulationofunrepaireddouble-strandbreaks(DSBs)[1].SCR7pyrazinetreatmentshowsadose-dependentdecreaseincellproliferationwithIC50valuesof40μM,34μM,44μM,8.5μM,120μM,10μMand50μMforMCF7,A549,HeLa,T47D,A2780,HT1080andNalm6cells,respectively[1].InMCF7cells,SCR7pyrazine(20,40μM)treatmentincreasesphosphorylationofATMandactivatesp53,decreasesMDM2,BCL2,resultinginactivationofproapoptoticproteins,PUMAandBAX.AndtheshorterfragmentsofMCL1,PARP1,Caspase3,andCaspase9cleavageareupregulatedinadose-dependentmanner[1].WesternBlotAnalysis[1]CellLine:MCF7cellsConcentration:20μM,40μM,100μMIncubationTime:24hoursResult:ShowedanincreaseinlevelsofgH2AXfociandprotein.體內(nèi)研究SCR7pyrazine(10mg/kg;intraperitonealinjection;sixdoses;BALB/cmice)treatmentsignificantlyreducesbreastadenocarcinoma-inducedtumorandincreaseslifespan[1].AnimalModel:BALB/cmiceinjectedwithbreastadenocarcinomacells[1]Dosage:10mg/kgAdministration:Intraperitonealinjection;onalternatedays(0,2,4,6,8,and10)Result:Significantlyreducedbreastadenocarcinoma-inducedtumorandincreasedlifespan.?EMBORep.2019Mar;20(3):e46821.?JImmunol.2020Feb19.pii:ji1900305.?JMolMed(Berl).2019Aug;97(8):1183-1193.?OncoTargetsTher.2018Aug17;11:4945-4953.Seemorecustomervalidationsonwww.MedChemE2/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemEREFERENCES[1].SrivastavaM,etal.Aninhibitorofnonhomologousend-joiningabrogatesdouble-strandbreakrepairandimpedescancerprogression.Cell.2012Dec21;151(7):1474-87.[2].LinC,etal.IncreasingtheEfficiencyofCRISPR/Cas9-mediatedPreciseGenomeEditingofHSV-1VirusinHumanCells.SciRep.2016Oct7;6:34531.McePdfHeightCaution:Producthasnotbeenfullyva