Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETGX-221Cat.No.:HY-10114CASNo.:663619-89-4分?式:C??H??N?O?分?量:364.44作?靶點:PI3K作?通路:PI3K/Akt/mTOR儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數據體外實驗DMSO:12.5mg/mL(34.30mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.7439mL13.7197mL27.4394mL5mM0.5488mL2.7439mL5.4879mL10mM0.2744mL1.3720mL2.7439mL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。-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?現配，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沉淀、析出現象，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%salineSolubility:≥1.25mg/mL(3.43mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1.25mg/mL(3.43mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.25mg/mL(3.43mM);ClearsolutionBIOLOGICALACTIVITY?物活性TGX-221?種?效的、選擇性的、細胞膜滲透的PI3Kp110β抑制劑，常?于癌癥研究。IC50&Targetp110βp110δ8.5nM(IC50)211nM(IC50)體外研究TGX-221,BL05andBL05-HAshowselectivecytotoxicitytoLNCaPcells,whichmaybeduetothedeficiencyofPTENinthiscelllineandtheaccumulationofPIP3inthecells[1].TGX-221(1μM)doesnotaffecttheexpressionandphosphorylationofAMPKinC2C12myoblasts[2].TGX221(0.1,1,10?μM)inducesIL-6releasefromASMcells[2].TGX-221doesnotaffectneurotensin-stimulatedAktphosphorylationwhenusedalone,butitfurthersuppressesneurotensin-stimulatedphosphorylationofAktwhencombinedwithgefitinib.TGX-221abolishestheneurotensin-stimulatedphosphorylationofAktinPanc-1cells[3].體內研究TGX-221(TGX221,2.5mg/kgi.v.)abolishescyclicflowreductionsinaFolts-likecarotidarterystenosispreparationofthrombosis,withoutchangingbleedingtime,heartrate,bloodpressureorcarotidvascularconductance[4].PROTOCOLCellAssay[1]TheprostatecancercelllinesDU145andLNCaParemaintainedinRPMI-1640medium,andPC3cellsaremaintainedinF-12Kmedium.LNCaPisaPSMApositivecellline,whereasDU145andPC3arePSMAnegative.Botharesupplementedwith10%fetalbovineserum.Cellsareplatedin96-wellflat-bottomedplatesataconcentrationof5,000cellsperwellin90μLofgrowthmedium.After12h,TGX-221,BL05,orBL05-HAloadedmicellesinPBSareaddedatconcentrationsof0,0.1,1,5,10,50or100μM.PBSand10μLoftrichloroaceticacid(TCA)areaddedtonegativeandpositivecontrolwells,respectively.After72h,10μLof55-μMresazurinblueisaddedtoeachwellandincubatedat37°Cfor4h.Afterincubation,theresorufinproductismeasuredwithafluorophotometerusinganexcitationwavelengthof560nmandanemissionwavelengthof590nm.TheIC50isdeterminedasthemidpointbetweenpositiveandnegativecontrolgroupsforeachplateusingGraphPadPrism5software.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalRatsarerandomLyassignedtodrugtreatmentgroupsconsistingofthevehiclepropyleneglycol(0.25Administration[4]mL/kg),LY294002(2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one;areversiblenon-specificPI3Kinhibitor;10mg/kg),wortmannin(anirreversiblenon-specificPI3Kinhibitor;5mg/kg),IC87114(2-[(6-aminopurin-9-yl)methyl]-5-methyl-3-(2-methylphenyl)quinazolin-4-one;aPI3Kp110δantagonist;2.5mg/kg)andtheselectivePI3Kp110βantagonistTGX221(2.5mg/kg).Inthetailbleedingexperiments,ratsare2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemErandomLyassignedtodrugtreatmentgroupsconsistingofLY294002(10mg/kg),IC87114(2.5mg/kg),wortmannin(5mg/kg),TGX221(2.5or25mg/kg),heparin(100U/kg),aspirin(2×200mg/kgp.o.)±heparin(100U/kg),andaspirin(2×200mg/kgp.o.)combinedwithheparin(100U/kg)andTGX221(2.5mg/kg).Alldrugs,withtheexceptionofaspirin,areadministeredasaslow(over≈45-60s)i.v.bolusof0.25mL/kgintothejugularvein.Aspirin(200mg/kgsuspendedin15%gumarabicinwater)isadministeredtwiceorally(p.o.)-thefirstdoseisgiven24hbeforetheexperimentandtheseconddose1hbeforethestartoftheexperiment.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產品發(fā)表的科研?獻?JClinInvest.2021Dec15;131(24):e140436.?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?CellSyst.2020Jan22;10(1):66-81.e11.?CellSyst.2020Jan22;10(1):66-81.e11.?EMBORep.2020Dec3;21(12):e49756.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ZhaoY,etal.ProdrugstrategyforPSMA-targeteddeliveryofTGX-221toprostatecancercells.MolPharm.2012Jun4;9(6):1705-16.[2].GeQ,etal.Thephosphoinositide3'-kinasep110δmodulatescontractileproteinproductionandIL-6releaseinhumanairwaysmoothmuscle.JCellPhysiol.2012Aug;227(8):3044-52.[3].MüllerKM,etal.RoleofproteinkinaseCandepidermalgrowthfactorreceptorsignallingingrowthstimulationbyneurotensinincoloncarcinomacells.BMCCancer.2011Oct2;11:421.[4].SturgeonSA,etal.Advantagesofaselectivebeta-isoformphosphoinositide3-kinaseantagonist,ananti-thromboticagentdevoidofothercardiovascularactionsintherat.EurJPharmacol.2008Jun10;587(1-3):209-15.[5].ChaussadeC,etal.Evidenceforfunctionalredundancyofclass