Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGDC-0575dihydrochlorideCat.No.:HY-112167ACASNo.:1657014-42-0Synonyms:ARRY-575dihydrochloride;RG7741dihydrochloride分?式:C??H??BrCl?N?O分?量:451.19作?靶點:CheckpointKinase(Chk)作?通路:CellCycle/DNADamage儲存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數據體外實驗DMSO:65mg/mL(144.06mM;Needultrasonic)H2O:25mg/mL(55.41mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.2164mL11.0818mL22.1636mL5mM0.4433mL2.2164mL4.4327mL10mM0.2216mL1.1082mL2.2164mL請根據產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，避免反復凍融造成的產品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C儲存時，請在6個?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?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：(為保證實驗結果的可靠性，澄的儲備液可以根據儲存條件，適當保存；體內實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.17mg/mL(4.81mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.17mg/mL(4.81mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.17mg/mL(4.81mM);ClearsolutionBIOLOGICALACTIVITY?物活性GDC-0575dihydrochloride(ARRY-575dihydrochloride)?種選擇性的，可?服的CHK1抑制劑，IC50值為1.2nM，具有抗腫瘤活性。IC50&TargetChk11.2nM(IC50)體外研究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].體內研究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,theyareirradiatedat6.8?Gyandtheculturemediaexchanged.Onday0oftheco-culture,AmLcellsareplatedat2?×?105cells/mLusingthecorrespondentAmLmedium.Cellsareculturedat37°Cin5%CO2-humidifiedincubatorsatindicatedoxygenconcentrations.Forshort-termculture(STC),cellsarekeptfor1weekinhypoxia(5%O2)withtheindicateddrugs:500?nMAraCand/or100?nMGDC-0575[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]NSGmiceareinjectedintravenouslywith1?×?105-106cellsofAmLand1-3?×?105cellsofhCBCD34+/hBMCD34+.AfterdemonstratingAmLengraftmentat9-11weeksthroughFACSanalysisoftibiabonemarrowaspiration,micearetreatedaccordinglytoproper7-daytreatmentregimenwithdaily10?mg/kgAraCviasubcutaneousinjection,7.5?mg/kgGDC-0575suspensionadministeredviaoralgavageoneveryotherday2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEschedule,and/or300?μg/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.戶使?本產品發(fā)表的科研?獻?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