Omipalisib-GSK2126458-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEOmipalisibCat.No.:HY-10297CASNo.:1086062-66-9Synonyms:GSK2126458;GSK458分?式:C??H??F?N?O?S分?量:505.5作?靶點(diǎn):PI3K;mTOR;Autophagy作?通路:PI3K/Akt/mTOR;Autophagy儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:50mg/mL(98.91mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.9782mL9.8912mL19.7824mL5mM0.3956mL1.9782mL3.9565mL10mM0.1978mL0.9891mL1.9782mL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(chǔ)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(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動(dòng)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(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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:≥2.5mg/mL(4.95mM);ClearsolutionBIOLOGICALACTIVITY?物活性O(shè)mipalisib(GSK2126458)?種?服有效的，?選擇性的PI3K抑制劑，抑制p110α/β/δ/γ，mTORC1/2的活性，Ki值分別為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)體外研究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].體內(nèi)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?邊的抑制劑?師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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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