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

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGDC-0575dihydrochlorideCat.No.:HY-112167ACASNo.:1657014-42-0Synonyms:ARRY-575dihydrochloride;RG7741dihydrochloride分⼦式:C₁₆H₂₂BrCl₂N₅O分⼦量:451.19作⽤靶点:CheckpointKinase(Chk)作⽤通路:CellCycle/DNADamage储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:65mg/mL(144.06mM;Needultrasonic)H2O:25mg/mL(55.41mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.2164mL11.0818mL22.1636mL5mM0.4433mL2.2164mL4.4327mL10mM0.2216mL1.1082mL2.2164mL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,awayfrommoisture)。-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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.17mg/mL(4.81mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.17mg/mL(4.81mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.17mg/mL(4.81mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性GDC-0575dihydrochloride(ARRY-575dihydrochloride)⼀种选择性的，可⼝服的CHK1抑制剂，IC50值为1.2nM，具有抗肿瘤活性。IC50&TargetChk11.2nM(IC50)体外研究GDC-0575dihydrochlorideisaselectiveandorallybioavailableCHK1inhibitor,withanIC50of1.2nM.GDC-0575(100nM)suppresssesCHK1activationinducedbyAraCbydecreasingthelevelofTyr15-phosphorylatedCDK2.GDC-0575(100nM)hasnoeffectontheviabilityofAMLcells,butsignificantlyreducescellviabilityandinducesapoptosisincombinationwithAraC.Inaddition,GDC-0575plusAraCshowsnoeffectonnormalhematopoieticstemandprogenitorcells(HSPCs)[1].GDC-0575showscytotoxicactivityagainstmostof20melanomacelllinestested,butseveralcelllinesgrownastumoursphere(TS)arerelativelyinsensitive[2].体内研究GDC-0575(7.5mg/kg,p.o.)incombinationwithAraCalomostcompletelyeradicatesleukemicburdeninmicetransplantedwithU937-Luccells,andshowsmoreefficientactivitythanAraCalone.Furthermore,GDC-0575elevatesthecytotoxicityofAraCindifferentprimaryAMLmodelsinvivo[1].GDC-0575(25,50mg/kg,p.o.)dose-dependentlyinhibitsthegrowthoftumorinD20andC002xenografts[2].PROTOCOLCellAssay[1]Forco-cultureexperiments,2daysbeforeinitiatingtheco-culture,feedercellsareplatedontotype-Icollagen-coated96-wellor6-wellplatesandallowedtoreachconfluence.Onedaybeforestartingco-culture,theyareirradiatedat6.8ꢀGyandtheculturemediaexchanged.Onday0oftheco-culture,AmLcellsareplatedat2ꢀ×ꢀ105cells/mLusingthecorrespondentAmLmedium.Cellsareculturedat37°Cin5%CO2-humidifiedincubatorsatindicatedoxygenconcentrations.Forshort-termculture(STC),cellsarekeptfor1weekinhypoxia(5%O2)withtheindicateddrugs:500ꢀnMAraCand/or100ꢀnMGDC-0575[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]NSGmiceareinjectedintravenouslywith1ꢀ×ꢀ105-106cellsofAmLand1-3ꢀ×ꢀ105cellsofhCBCD34+/hBMCD34+.AfterdemonstratingAmLengraftmentat9-11weeksthroughFACSanalysisoftibiabonemarrowaspiration,micearetreatedaccordinglytoproper7-daytreatmentregimenwithdaily10ꢀmg/kgAraCviasubcutaneousinjection,7.5ꢀmg/kgGDC-0575suspensionadministeredviaoralgavageoneveryotherday2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEschedule,and/or300ꢀμg/kgG-CSFadministereddailyfor5daysviaintraperitonealinjection.Oneweekafterthefinaldosing,micearekilledbycervicaldislocation.Thefemurs,tibias,andpelvisaredissectedandflushedwithPBS.Redbloodcellsarelyzedviaammoniumchloride.Cellsarestainedwithhuman-specificFITC-conjugatedanti-CD19,PE-conjugatedanti-CD33,PE-Cy7-conjugatedanti-CD45,andPERCP-conjugatedanti-murineCD45antibodies.DeadcellsanddebrisareexcludedviaDAPIstaining.ABDLSRIIflowcytometerisusedforanalysis.FlowcytometryanalysisisperformedwithFlowJosoftware.Morethan100,000DAPI-negativeeventsarecollected.EngraftmentofAmLissaidtobepresentifasinglepopulationofmCD45-hCD45+CD33+CD19-cellsispresentwithoutaccompanyingmCD45-hCD45+CD33−CD19+cells[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•NatCommun.2020Jan8;11(1):123.•Neurotherapeutics.2022Mar;19(2):570-591.•MolCancerRes.2020Jan;18(1):91-104.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].DiTullioA,etal.ThecombinationofCHK1inhibitorwithG-CSFoverridescytarabineresistanceinhumanacutemyeloidleukemia.NatCommun.2017Nov22;8(1):1679.[2].OoZY,etal.EndogenousReplicationStressMarksMelanomasSensitivetoCHEK1InhibitorsIn