Vistusertib-AZD2014-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEVistusertibCat.No.:HY-15247CASNo.:1009298-59-2Synonyms:AZD2014分?式:C??H??N?O?分?量:462.54作?靶點(diǎn):mTOR;Autophagy;Apoptosis作?通路:PI3K/Akt/mTOR;Autophagy;Apoptosis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(108.10mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.1620mL10.8099mL21.6198mL5mM0.4324mL2.1620mL4.3240mL10mM0.2162mL1.0810mL2.1620mL請(qǐng)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(qǐng)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(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)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(qǐng)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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.40mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(5.40mM);Suspendedsolution;Needultrasonicandwarming3.請(qǐng)依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:2.5mg/mL(5.40mM);Suspendedsolution;Needultrasonic4.請(qǐng)依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(5.40mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Vistusertib(AZD2014)?種ATP競(jìng)爭(zhēng)性的mTOR抑制劑，IC50為2.81nM。AZD2014抑制mTORC1和mTORC2復(fù)合物。IC50&TargetmTORmTORC1mTORC2PI3Kα2.81nM(IC50)3.766μM(IC50)Autophagy體外研究TheinhibitoryeffectsofVistusertib(AZD2014)aremeasuredagainstisolatedrecombinantmTORenzyme(IC50of2.81nM)aswellasincellularassaysmeasuringbothmTORC1andmTORC2activities.InMDAMB468cells,Vistusertib(AZD2014)decreasesthephosphorylationofthemTORC1substrateribosomalproteinS6(Ser235/236)withameanIC50valueof210nMandthemTORC2substrateAKT(Ser473)withameanIC50valueof78nM[1].體內(nèi)研究Vistusertib(AZD2014)inducesdose-dependenttumorgrowthinhibitioninseveralxenograftandprimaryexplantmodels.TheantitumoractivityofVistusertib(AZD2014)isassociatedwithmodulationofbothmTORC1andmTORC2substrates,consistentwithitsmechanismofaction.ThepharmacokineticsofVistusertib(AZD2014)inmiceistesteduponadministrationofdosesbetween7.5and15mg/kg.Adose-dependentincreaseinCmaxandAUCisobservedfollowingsingledoseandrepeatdosingofAZD2014:Cmaxrangefrom1to16μMandAUCrangefrom220to5,042μM·hacrossthisdoserange.ThepharmacodynamiceffectofVistusertib(AZD2014)againstanmTORC1biomarker(phosphorylationofS6)andanmTORC2biomarker(phosphorylationofAKT)isassessedinSCIDmicebearingMCF7xenograftsfollowingadministrationof3.75,7.5,and15mg/kgAZD2014.Thereisagoodrelationshipbetweenthedrugplasmaconcentrationsandbiomarkerlevels(estimatedp-AKTIC50of0.119μMtotal,53%SE,andestimatedp-S6IC500.392μM,28.8%SE)[1].PROTOCOLAnimalMice[1]Administration[1]MCF7experiments:5×106MCF7cellsareinjecteds.c.inavolumeof0.1mLinmaleSCIDmiceandarerandomizedintocontrolandtreatmentgroupswhentumorsizereach0.2cm3.Vistusertib(AZD2014)is2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEdissolvedincaptisol,anddilutedtoafinalcaptisolconcentrationof30%(w/v).Vistusertib(AZD2014)isadministeredbyoralgavage(0.1mL/10gbodyweight).Thecontrolgroupreceivevehicleonly.Tumorvolumes(measuredbycalliper),animalbodyweightandconditionarerecordedtwiceweeklyforthedurationofthestudy.Thetumorvolumeiscalculated(takinglengthtobethelongestdiameteracrossandwidthtobethecorrespondingperpendiculardiameter)usingtheformula:(length×width)×√(length×width)×(π/6).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Science.2017Dec1;358(6367):eaan4368.?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?NatCommun.2019Jul1;10(1):2901.?NatCommun.2017Jun8;8:15617.?Autophagy.2021Jun;17(6):1349-1366.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].GuichardSM,etal.AZD2014,aninhibitorofmTORC1andmTORC2,ishighlyeffectiveinER+breastcancerwhenadministeredusingintermittentorcontinuousschedules.MolCancerTher.2015Nov;