ART558-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEART558Cat.No.:HY-141520CASNo.:2603528-97-6分⼦式:C₂₁H₂₁F₃N₄O₂分⼦量:418.41作⽤靶点:Others作⽤通路:Others储存⽅式:4°C,sealedstorage,awayfrommoistureandlight*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoistureandlight)溶解性数据体外实验DMSO:170mg/mL(406.30mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.3900mL11.9500mL23.9000mL5mM0.4780mL2.3900mL4.7800mL10mM0.2390mL1.1950mL2.3900mL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(sealedstorage,awayfrommoistureandlight)。-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.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:4.25mg/mL(10.16mM);Suspendedsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥5mg/mL(11.95mM);Clearsolution1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性ART558⼀种纳尔、⾼效、有选择性、低分⼦量、变构DNA聚合酶活性的Polθ抑制剂(IC50=7.9nM)。ART558可⽤于癌症研究[1]。IC50&TargetIC50:7.9nM(Polθ)[1]体外研究ART558(0~10μM;7days;BRCA2wild-typeorBRCA2‒/‒cells)showssyntheticlethalityandacombinatorialeffectwiththePARPiolaparibinpreviouslydescribedisogenicmodelsofBRCA1-deficiency[1].ART558(5μM;0~72hours;BRCA2wild-typeorBRCA2‒/‒cells)showsγH2AXaccumulationincells[1].ART558inhibitsthemajorPolθmediatedDNArepairprocess,Theta-MediatedEndJoining,withouttargetingNonHomologousEndJoining.ART558elicitsDNAdamageandsyntheticlethalityinBRCA1-orBRCA2-mutanttumourcellsandenhancestheeffectsofaPARPinhibitor.ART558increasesbiomarkersofsingle-strandedDNAandsyntheticlethalityin53BP1-defectivecellswhilsttheinhibitionofDNAnucleasesthatpromoteend-resectionreversedtheseeffects,implicatingtheseinthesyntheticlethalmechanism-of-action.ART558increasestheresidencetimeofYFP-taggedfull-lengthPolθatsitesoflaserinducedDNAdamage[1].CellViabilityAssay[1]CellLine:BRCA2wild-typeorBRCA2‒/‒cellsConcentration:0~10μMIncubationTime:7daysResult:ShowedsyntheticlethalityandacombinatorialeffectwiththePARPiolaparibinpreviouslydescribedisogenicmodelsofBRCA1-deficiency.WesternBlotAnalysis[1]CellLine:BRCA2wild-typeorBRCA2‒/‒cellsConcentration:5μMIncubationTime:0~72hoursResult:ShowedγH2AXaccumulationincells.REFERENCES[1].ZatreanuD,etal.PolθinhibitorselicitBRCA-genesyntheticlethalityandtargetPARPinhibitorresistance.NatCommun.2021Jun17;12(1):3636.McePdfHigtCaution:Producthasnotbeenfullyvalidatedformedicalap