Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAlisertibCat.No.:HY-10971CASNo.:1028486-01-2Synonyms:MLN8237分?式:C??H??ClFN?O?分?量:518.92作?靶點(diǎn):AuroraKinase;Autophagy;Apoptosis作?通路:CellCycle/DNADamage;Epigenetics;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:25mg/mL(48.18mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.9271mL9.6354mL19.2708mL5mM0.3854mL1.9271mL3.8542mL10mM0.1927mL0.9635mL1.9271mL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.請(qǐng)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:2.08mg/mL(4.01mM);Suspendedsolution;Needultrasonic2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(4.01mM);Suspendedsolution;Needultrasonic3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.01mM);ClearsolutionBIOLOGICALACTIVITY?物活性Aliertib(MLN8237)?種?服活性和選擇性的AuroraA激酶抑制劑(IC50=1.2nM)，與AuroraA激酶結(jié)合，導(dǎo)致有絲分裂紡錘體異常、有絲分裂累積。Aliertib(MLN8237)通過靶向??病細(xì)胞中的AKT/mTOR/AMPK/p38途徑誘導(dǎo)其凋亡和?噬。具有抗腫瘤活性[1][2][3]。IC50&TargetAuroraAAuroraB1.2nM(IC50)396.5nM(IC50)體外研究Alisertib(MLN8237)leadstheMMcellstomitoticspindleabnormalities,mitoticaccumulation,aswellasinhibitionofcellproliferationthroughapoptosisandsenescence.Alisertibup-regulatesp53andtumorsuppressorgenesp21andp27[1].ThedecreasedactivityofAlisertib(MLN8237)fortheT217D/W277EAuroraA/TPX2complexmayreflecttheincreasedaffinityforATPinducedbycofactorbindingtoAuroraA[2].Alisertib(MLN8237)inhibitscellproliferationwithIC50srangingfrom15to469nMindifferenttumercelllines[4].體內(nèi)研究Alisertib(MLN8237)(30mg/kg,p.o.)significantlyreducestumorburdenandincreasesoverallsurvivalinxenograft-murinemodelofhuman-MM[1].Alisertib(3-30mg/kg;p.o.;oncedailyfor3weeks)causestumorgrowthinhibitioninsolidtumorxenograftmodels[4].AnimalModel:NudemicebearingHCT-116colontumorxenograft[4]Dosage:3,10,or30mg/kgAdministration:P.o.;oncedailyfor3weeksResult:Resultedinadose-dependentTGI(tumorgrowthinhibition)of43.3%,84.2%,and94.7%forthe3,10,and30mg/kggroups,respectively.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Cell.2017Jan12;168(1-2):264-279.e15.?JHepatol.2021Aug;75(2):363-376.?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?ClinCancerRes.2019Jul1;25(13):4179-4193.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE?Theranostics.2018Feb12;8(6):1740-1751.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].GüllüG,etal.AnovelAurora-AkinaseinhibitorMLN8237inducescytotoxicityandcell-cyclearrestinmultiplemyelomaBloodJune24,2010vol.115no.255202-5213.[2].SloaneDA,etal.Drug-ResistantAuroraAMutantsforCellularTargetValidationoftheSmallMoleculeKinaseInhibitorsMLN8054andMLN8237ACSChem.Biol.,2010,5(6),pp563-576.[3].BavetsiasV,etal.AuroraKinaseInhibitors:CurrentStatusandOutlook.FrontOncol.2015Dec21;5:278.[4].ManfrediMG,etal.CharacterizationofAlisertib(MLN8237),aninvestigationalsmall-moleculeinhibitorofauroraAkinaseusingnovelinvivopharmacodynamicassays.ClinCancerRes.2011Dec15;17(24):7614-7624.McePdfHeightCaution:Produc