Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGDC-0575Cat.No.:HY-112167CASNo.:1196541-47-5Synonyms:ARRY-575;RG7741分?式:C??H??BrN?O分?量:378.27作?靶點:CheckpointKinase(Chk)作?通路:CellCycle/DNADamage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(264.36mM;Needultrasonic)H2O:<0.1mg/mL(insoluble)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.6436mL13.2181mL26.4361mL5mM0.5287mL2.6436mL5.2872mL10mM0.2644mL1.3218mL2.6436mL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，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。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。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(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(6.61mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.61mM);ClearsolutionBIOLOGICALACTIVITY?物活性GDC-0575(ARRY-575,RG7741)?選擇性，有?服活性的?分?Chk1抑制劑，其在異種移植模型中導(dǎo)致腫瘤縮?和?長延遲，IC50值為1.2nM。IC50&Target1.2?nM(Chk1)[1]體外研究GDC-0575issignificantlymorepotentinpromotingDNAdamage,replicationstressandcelldeaththanV158411,LY2603618,andMK-8776inapanelofmelanomacelllines[1].GDC-0575abrogatesDNAdamage-inducedSandG2–Mcheckpoints,exacerbatesDNAdouble-strandbreaksandinducesapoptosisinSTScells.GDC-0575hasasynergisticoradditiveeffecttogetherwithgemcitabine[2].CHK1inhibitorGDC-0575incombinationwithAraCenhancesthekillingofprimaryacutemyeloidleukemiacellsexvivobyinducingapoptosis[3].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NatCommun.2020Jan8;11(1):123.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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