GDC-0575-ARRY-575-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGDC-0575Cat.No.:HY-112167CASNo.:1196541-47-5Synonyms:ARRY-575;RG7741分⼦式:C₁₆H₂₀BrN₅O分⼦量:378.27作⽤靶点:CheckpointKinase(Chk)作⽤通路:CellCycle/DNADamage储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(264.36mM;Needultrasonic)H2O:<0.1mg/mL(insoluble)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.6436mL13.2181mL26.4361mL5mM0.5287mL2.6436mL5.2872mL10mM0.2644mL1.3218mL2.6436mL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。-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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(6.61mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.61mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性GDC-0575(ARRY-575,RG7741)⾼选择性，有⼝服活性的⼩分⼦Chk1抑制剂，其在异种移植模型中导致肿瘤缩⼩和⽣长延迟，IC50值为1.2nM。IC50&Target1.2ꢀnM(Chk1)[1]体外研究GDC-0575issignificantlymorepotentinpromotingDNAdamage,replicationstressandcelldeaththanV158411,LY2603618,andMK-8776inapanelofmelanomacelllines[1].GDC-0575abrogatesDNAdamage-inducedSandG2–Mcheckpoints,exacerbatesDNAdouble-strandbreaksandinducesapoptosisinSTScells.GDC-0575hasasynergisticoradditiveeffecttogetherwithgemcitabine[2].CHK1inhibitorGDC-0575incombinationwithAraCenhancesthekillingofprimaryacutemyeloidleukemiacellsexvivobyinducingapoptosis[3].体内研究GDC-0575isactiveat25mg/kgasasingleagent,buttheefficacyisimprovedatthehigherdrugdose.GDC-0575effectivelyblockstumorgrowthintheD20andC002xenografts,andtheeffectismaintainedforatleast10daysafterthefinaldoseisadministered[1].PROTOCOLCellAssay[3]AMLcelllinesareseededat1×104cells/wellin96-wellplatesintriplicate,andsubjectedtodifferenttreatmentconditions.After24hofincubationwithGDC-0575,cellproliferationismeasuredwiththeXTTCellProliferationKitII[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]FemalenudeBALB/cmiceareinjectedwith2-3×106melanomacellsinMatrigelbysubcutaneousinjectiononthehindflank.Oncetumorsreachapproximately100mm3,micearetreatedwithGDC-0575(25mg/kg,50mg/kg)orvehicle(0.5%w/vmethylcelluloseand0.2%v/vTween80)byoralgavagefor3cycleswhereonecycleisthreeconsecutivedaysoftreatmentfollowedbyfourrestdays.Tumorsizeismeasuredthreetimesperweekusingcalipers.Micearesacrificedatupto6weeksafterterminatingthetreatmentorwhentumorsizemeasured>1cm3[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•NatCommun.2020Jan8;11(1):123.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•Neurotherapeutics.2022Mar;19(2):570-591.•MolCancerRes.2020Jan;18(1):91-104.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].OoZY,etal.EndogenousReplicationStressMarksMelanomasSensitivetoCHEK1InhibitorsInVivo.ClinCancerRes.2018Mar13.doi:10.1158/1078-0432.CCR-17-2701.[2].Laroche-ClaryA,etal.CHK1inhibitioninsoft-tissuesarcomas:biologicalandclinicalimplications.AnnOncol.2018Apr1;29(4):1023-1029.[3].DiTullioA,etal.ThecombinationofCHK1inhibitorwithG-CSFoverridescytarabineresistanceinhumanacutemyeloidleukemia.NatCommun.2017Nov22;8(1):1679.McePdfHeightCauti