GSK-1070916-GSK-1070916A-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGSK-1070916Cat.No.:HY-70044CASNo.:942918-07-2Synonyms:GSK-1070916A分?式:C??H??N?O分?量:507.63作?靶點:AuroraKinase;Apoptosis作?通路:CellCycle/DNADamage;Epigenetics;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:16.67mg/mL(32.84mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.9699mL9.8497mL19.6994mL5mM0.3940mL1.9699mL3.9399mL10mM0.1970mL0.9850mL1.9699mL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.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:≥1.67mg/mL(3.29mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1.67mg/mL(3.29mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1mg/mL(1.97mM);ClearsolutionBIOLOGICALACTIVITY?物活性GSK-1070916有效，選擇性，ATP競爭型的極光激酶B/C(auroraB/C)抑制劑，Ki值分別為0.38和1.5nM。IC50&TargetAuroraBAuroraC0.38nM(Ki)1.5nM(Ki)體外研究GSK-1070916potentlyinhibitsAuroraB/INCENPandAuroraC/INCENPkinaseswithKisof0.38±0.29and1.45±0.35nM,respectively,butislesspotentagainstAuroraA/TPX2withaKiof492±61nM.GSK-1070916alsoinhibitsFLT1,TIE2,SIK,FLT4,andFGFR1withIC50valuesof42,59,70,74,and78nM,respectively.TreatmentofA549humanlungcancercellswithGSK-1070916resultsinapotentantiproliferativeeffect(EC50=7nM)[1].GSK-1070916inhibitsapaneloftumorcelllinesandisshownoinhibitsthephosphorylationofHH3-S10inallcelllineswithaverageEC50valuesrangingfrom8to118nM[2].體內(nèi)研究Innudemiceimplantedwithhumancolontumor(HCT116)xenografts,asingledoseofGSK-1070916administeredi.p.inhibitsHH3-S10phosphorylationinadose-dependentmanner.Repeatedi.p.administrationofGSK-1070916producescompleteorpartialantitumoractivityin4of8tumortypes[lung,A549;colon,HCT116;acutemyelogenousleukemia(AML),HL60;andchronicmyelogenousleukemia,K562],stablediseasein3of8(colon,Colo205;lung,H460;andbreast,MCF-7),andtumorgrowthdelayin1of8tumortypes(colon,SW620).DailyadministrationofGSK-1070916isgenerallywell-tolerated[2].PROTOCOLCellAssay[2]Apaneloftumorcelllinesareplatedin96-wellplatesintherecommendedgrowthmediaandincubatedat37°Cin5%CO2overnight.Thefollowingday,thecellsaretreatedwithserialdilutionsofGSK-1070916.Atthistime,onesetofcellsistreatedwithCellTiter-Gloforatimeequalto0(T=0)measurement.Followinga6-to7-dincubationwithcompound,cellproliferationismeasuredusingtheCellTiter-Gloreagent[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:Tumorsareinitiatedbyinjectionoftumorcellsuspensions(A549,SW620,HCT116,H460,MCF-7,Administration[2]HL60,K562)ortumorfragments(Colo205)onude(A549,SW620,HCT116,H460,MCF-7,HL60,andColo205)orseverecombinedimmunodeficient(SCID;K562)mice.Whenthetumorsreachavolumeof80to200mm3,themicearerandomizedintogroupsof5to10micepergroup.GSK-1070916isadministeredat25,50,or100mg/kgoncedailyfor5consecutivedays-on,2d-off,schedulefortwo(Colo205andHL60)orthree(A549,SW620,HCT116,H460,MCF-7,K562)cycles.Tumorsaremeasuredtwiceweekly[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?JBiomolScreen.2013Oct;18(9):1062-71.?HarvardMedicalSchoolLINCSLIBRARYSeemorecustomervalidationsonwww.MedChemEREFERENCES[1].AdamsND,etal.DiscoveryofGSK-1070916,apotentandselectiveinhibitorofAuroraB/Ckinase.JMedChem.2010May27;53(10):3973-4001.[2].HardwickeMA,etal.GSK-1070916,apotentAuroraB/Ckinaseinhibitorwithbroadantitumoractivityintissueculturecellsandhumantumorxenograftmodels.MolCancerTher.2009Jul