Miransertib-ARQ-092-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMiransertibCat.No.:HY-19719CASNo.:1313881-70-7Synonyms:ARQ-092分?式:C??H??N?分?量:432.52作?靶點(diǎn):Akt;Parasite作?通路:PI3K/Akt/mTOR;Anti-infection儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:12.5mg/mL(28.90mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.3120mL11.5602mL23.1203mL5mM0.4624mL2.3120mL4.6241mL10mM0.2312mL1.1560mL2.3120mL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(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲存時(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，澄的儲備液可以根據(jù)儲存條件，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:≥1.25mg/mL(2.89mM);ClearsolutionBIOLOGICALACTIVITY?物活性Miransertib(ARQ-092)?種有效的，具有?服活性的，選擇性和變構(gòu)性Akt抑制劑，對Akt1，Akt2，Akt3的IC50分別為2.7nM，14nM和8.1nM。Miransertib還有效的AKT1-E17K突變蛋?抑制劑，并可?于PI3K/AKT驅(qū)動(dòng)的腫瘤和Proteus綜合征的研究。Miransertib有效抑制利什曼原?(Leishmania)。IC50&TargetAkt1LeishmaniaAkt3Akt22.7nM(IC50)8.1nM(IC50)14nM(IC50)Akt1E17Kmutant體外研究Inalargepanelofcelllinesderivedfromvarioustumortypes,Miransertib(ARQ-092;Compound21a)showspotentanti-proliferativeactivityincelllinescontainingPIK3CA/PIK3R1mutationscomparedtothosewithwild-type(wt)PIK3CA/PIK3R1orPTENloss.Miransertibshowsexcellentinhibitionofp-Akt(S473)andp-Akt(T308)inbothAN3CAandA2780cells.Theinhibitionofthedownstreamproteinp-PRAS40(T246)isobservedwithMiransertib(IC50=0.31μM)[1].MiransertibismarkedlyeffectiveagainstintracellularamastigotesofL.donovaniorL.amazonensis-infectedmacrophages.MiransertibalsoenhancesmTORdependentautophagyinLeishmania-infectedmacrophages[2]體內(nèi)研究Miransertib(ARQ-092;Compound21a)showsgoodabsoluteoralbioavailabilityinrats(5mg/kg)andmonkeys(10mg/kg)withFvaluesof62%and49%,respectively.Thehalf-lifeislongerinratscomparedtomonkeyswitht1/2valuesof17hinratsversus7hinmonkeys.TheCmaxis198ng/mLand258ng/mLandtheAUCinfwas5496h?ng/mLand2960h?ng/mLinratsandmonkeys,respectively[1].Miransertib(ARQ-092;Compound21a)inhibitstumorgrowthinahumanxenograftmousemodelofendometrialadenocarcinoma[1].PROTOCOLCellAssay[1]Anti-proliferativecellularassaysareconductedusingtheCellTiterNon-RadioactiveCellProliferationAssay,whichutilizestheproductionofformazanfromatetrazoliumcompoundbylivecells.AN3CAandA2780cellsareobtainedfromtheATCC.AN3CAcellsareculturedinDMEM,andA2780cellsareculturedinRPMI.Cellsareplatedin96-wellplatesat2,000-10,000cells/well,culturedfor24h,andtreatedwiththetestcompoundfor72hatafinalDMSOconcentrationnogreaterthan0.5%v/v.PMSstockreagent(0.92mg/mLinDPBS)isdiluted20-foldinMTSstockreagent(2mg/mLinDPBS),andthisMTS/PMSmixtureisdiluted5-foldintoeachwellofthe96-wellplate.Theplatesareincubatedfor3-4h,andtheabsorbanceofformazanismeasuredat490nm.Thedataarenormalizedtotheuntreatedcontrols,thedose-responsecurvesarefittoafour-parameterlogisticequation,andtheIC50valuesaredetermined.AllIC50valuesreportedarethegeometricmeanofatleasttwoindependentdeterminations[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalMice[2]Administration[2]SHP2Y279C/+miceareused.OnlymaleprogenyareusedfortheexperimentshereinandallmicearemaintainedonoutbredC57BL6/Jbackgrounds,backcrossedformorethan10generations.EithervehicleorMiransertib(100mg/kgbodyweight)isthendailyadministeredbyoralgavagefor4weeks.Administrationbeganat12weeksofage(afterestablishedhypertrophyisindicated),andcontinuedfor4weeks,untilthemicereach16weeksofage.Ascontrols,SHP2+/+andSHP2Y279C/+micearetreatedwithvehiclealone.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?FASEBJ.2022Aug;36(8):e22423.?HumMolGenet.2022Aug22;ddac201.?Biomedicines.2022,10(7),1476.?UniversityofNorthCarolina.SchoolofMedicine,CurriculuminGeneticsandMolecularBiology2021Aug.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LapierreJM,etal.Discoveryof3-(3-(4-(1-Aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine(ARQ092):AnOrallyBioavailable,Selective,andPotentAllostericAKTInhibitor.JMedChem.2016Jul14;59(13):6455-69.[2].DevkiNandan,etal.Miransertib(ARQ092),anorally-available,selectiveAktinhibitoriseffectiveagainstLeish