Omipalisib-GSK2126458-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEOmipalisibCat.No.:HY-10297CASNo.:1086062-66-9Synonyms:GSK2126458;GSK458分⼦式:C₂₅H₁₇F₂N₅O₃S分⼦量:505.5作⽤靶点:PI3K;mTOR;Autophagy作⽤通路:PI3K/Akt/mTOR;Autophagy储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:50mg/mL(98.91mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.9782mL9.8912mL19.7824mL5mM0.3956mL1.9782mL3.9565mL10mM0.1978mL0.9891mL1.9782mL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.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:≥2.5mg/mL(4.95mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Omipalisib(GSK2126458)⼀种⼝服有效的，⾼选择性的PI3K抑制剂，抑制p110α/β/δ/γ，mTORC1/2的活性，Ki值分别为0.019nM/0.13nM/0.024nM/0.06nM和0.18nM/0.3nM。Omipalisib具有抗癌活性。IC50&Targetp110αp110α-E545Kp110α-E542Kp110α-H1047R0.019nM(Ki)0.008nM(Ki)0.008nM(Ki)0.009nM(Ki)p110βp110δp110γmTORC10.13nM(Ki)0.024nM(Ki)0.06nM(Ki)0.18nM(Ki)mTORC20.3nM(Ki)体外研究Omipalisib(GSK2126458)potentlyinhibitstheactivityofcommonactivatingmutantsofp110α(E542K,E545K,andH1047R)foundinhumancancerwithKiof8pM,8pMand9pM,respectively.OmipalisibcausesasignificantreductioninthelevelsofpAkt-S473withremarkablepotencyinT47DandBT474cellswithIC50of0.41nMand0.18nM,respectively.Furthermore,Omipalisib(GSK2126458)leadstoaG1cellcyclearrestandproducestheinhibitoryeffectoncellproliferationinalargepanelofcelllines,includingT47DandBT474breastcancerlineswithIC50of3nMand2.4nM,respectively[1].ThecombinationofOmipalisiborGSK1120212withOmipalisibenhancescellgrowthinhibitionanddecreasesS6ribosomalproteinphosphorylationindrug-resistantclonesfromtheA375BRAF(V600E)andtheYUSIT1BRAF(V600K)melanomacelllines[2].Omipalisib(GSK2126458)potentiatestheantiproliferativeactivityofDDR1-IN-1incolorectalcancercelllines[3].体内研究InaBT474humantumorxenograftmodel,Omipalisib(GSK2126458)treatmentresultsinadose-dependentreductioninpAkt-S473levels,andexhibitsdose-dependenttumorgrowthinhibitionatalowdoseof300μg/kg.Besides,Omipalisib(GSK2126458)showslowbloodclearanceandgoodoralbioavailabilityinfourpreclinicalspecies(mouse,rat,dog,andmonkey)[1].PROTOCOLCellAssay[1]BT474,HCC1954andT-47D(humanbreast)areculturedinRPMI-1640containing10%fetalbovineserumat37°Cin5%CO2incubator.CellsaresplitintoT75flasktwotothreedayspriortoassaysetupatdensitywhichyieldsapproximately70-80%confluenceattimeofharvestforassay.Cellsareharvestedusing0.25%trypsin-EDTA.CellcountsareperformedoncellsuspensionusingTrypanBlueexclusionstaining.Cellsarethenplatedin384wellblackflatbottompolystyrenein48μLofculturemediaperwellat1,000cells/well.Allplatesareplacedat5%CO2,37°CovernightandOmipalisib(GSK2126458)isaddedthefollowingday.OneplateistreatedwithCellTiter-Gloforaday0(t=0)measurementandreadasdescribedbelow.Omipalisib(GSK2126458)ispreparedinclearbottompolypropylene384wellplateswithconsecutivetwofolddilutions.4μLofthesedilutionsareaddedto105μLculturemedia,aftermixingthesolution,2μLofthesedilutions2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEareaddedintoeachwellofthecellplates.ThefinalconcentrationofDMSOinallwellsis0.15%.Cellsareincubatedat37°C,5%CO2for72hours.Following72hoursofincubationwithOmipalisibeachplateisdevelopedandread.CellTiter-Gloreagentisaddedtoassayplatesusingavolumeequivalenttothecellculturevolumeinthewells.Platesareshakenforapproximatelytwominutesandincubatedatroomtemperatureforapproximately30minutesandchemiluminescentsignalisreadontheAnalystGTreader.Resultsareexpressedasapercentofthet=0andplottedagainsttheOmipalisib(GSK2126458)concentration.CellgrowthinhibitionisdeterminedforOmipalisib(GSK2126458)byfittingthedoseresponsewitha4or6parametercurvefitusingXLfitsoftwareanddeterminingtheconcentrationthatinhibits50%ofthecellgrowth(gIC50)withtheYminasthet=0andYmaxastheDMSOcontrol.Valuefromwellswithnocellsissubtractedfromallsamplesforbackgroundcorrection..MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•JHepatol.2021Aug;75(2):363-376.•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•ClinCancerRes.2014Nov1;20(21):5483-95.•CellSyst.2020Jan22;10(1):66-81.e11.•CellSyst.2020Jan22;10(1):66-81.e11.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].KnightSD,etal.DiscoveryofGSK2126458,aHighlyPotentInhibitorofPI3KandtheMammalianTargetofRapamycin.ACSMed.Chem.Lett.2010,1(1),39-43.[2].GregerJG,etal.CombinationsofBRAF,MEK,andPI3K/mTORinhibitorsovercomeacquiredresistancetotheBRAFinhibitorGSK2118436dabrafenib,mediatedbyNRASorMEKmutations.MolCancerTher.2012Apr;11(4):909-20.[3].KimHG,etal.DiscoveryofapotentandselectiveDDR1rece