MBQ-167-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMBQ-167Cat.No.:HY-112842CASNo.:2097938-73-1分?式:C??H??N?分?量:338.41作?靶點(diǎn):Ras;CDK作?通路:GPCR/GProtein;CellCycle/DNADamage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:155mg/mL(458.02mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.9550mL14.7750mL29.5500mL5mM0.5910mL2.9550mL5.9100mL10mM0.2955mL1.4775mL2.9550mL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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.58mg/mL(7.62mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:2.58mg/mL(7.62mM);Clearsolution;NeedwarmingBIOLOGICALACTIVITY?物活性MBQ-167Ras相關(guān)的C3型?毒素底物(Rac)和細(xì)胞分裂周期蛋?(Cdc42)的雙抑制劑，其對(duì)Rac1/2/3的IC50值為103nM，對(duì)Cdc42的IC50值為78nM。IC50&TargetCdc42Ras1/2/378nM(IC50)103nM(IC50)體外研究MBQ-167(≥100nM)inducesalossofpolarityinmetastaticbreastcancercells.Treatmentwith500nMMBQ-167for24hresultsin~95%cellroundinganddetachmentfromthesubstratuminmetastaticMDA-MB-231cells.Moreover,MBQ-167inducesthisphenotypeinmultiplemesenchymalcancercelltypesincludingGFP-HER2-BM,MDA-MB-468,andHs578thumanbreastcancercells,aswellasMia-PaCa-2pancreaticcancercells,SKOV3ovariancancercells,AGSandNCI-N87gastriccancercells,andSH-SY5Yneuroblastomacells.Followingtreatmentwith250nMMBQ-167for24h,theattachedpopulationofMDA-MB-231cellsdemonstratea~25%decreaseinRacactivationwhilethedetachedcellsaremoreresponsivewitha~75%decrease.Atearliertimes(6h),treatmentwith250or500nMMBQ-167,induceainhibitioninRacactivityintheattachedcellpopulation,whilethedetachedpopulationdemonstratea~40-50%inhibition[1].體內(nèi)研究MBQ-167-treatedmicedemonstrateastatisticallysignificantreductionintumorgrowth.Atsacrifice,1.0mg/kgBWofMBQ-167resultsina~80%reductionintumorgrowth,andthe10mg/kgBWMBQ-167treatmentresultsin~95%reductionintumorgrowth.SinceEHop-016onlyexerts~40%reductionoftumorgrowthat10mg/kgBW,MBQ-167is10XmoreeffectivethanEHop-016.MBQ-167treatedmicedemonstratesimilardoublingtimesforbothtreatments(10and11days)[1].PROTOCOLAnimalMice[1]Administration[1]Femaleathymicnu/numice,4to5wkoldareused.GFP-HER2-BMcells(~5×105)inMatrigelareinjectedatthefourthrightmammaryfatpadunderisofluoraneinhalationtoproduceorthotopicprimarytumors.Aftertumorestablishment(1wkpost-inoculation),animalsarerandomlydividedintotreatmentgroups(n=6).Micearetreatedwithvehicle(12.5%ethanol,12.5%Cremophor,and75%1XPBSpH7.4),or1or10mg/kgBWMBQ-167byi.p.injectionina100μLvolume3Xawk.Treatmentscontinueuntilsacrificeatday65[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Nature.2022Oct;610(7931):366-372.?ClinTranslMed.2022Jun;12(6):e850.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESeemorecustomervalidationsonwww.MedChemEREFERENCES[1].Humphries-BickleyT,etal.CharacterizationofaDualRac/Cdc42InhibitorMBQ-167inMetastaticCancer.MolCancerTher.2017May;16(5):805-818.McePdfHeightCaution:Produ