MMAF-Monomethylauristatin-F-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMMAFCat.No.:HY-15579CASNo.:745017-94-1Synonyms:MonomethylauristatinF分⼦式:C₃₉H₆₅N₅O₈分⼦量:731.96作⽤靶点:Microtubule/Tubulin;ADCCytotoxin作⽤通路:CellCycle/DNADamage;Cytoskeleton;Antibody-drugConjugate/ADCRelated储存⽅式:4°C,sealedstorage,awayfrommoisture*该产品在溶液状态不稳定，建议您现⽤现配，即刻使⽤。溶解性数据体外实验DMSO:140mg/mL(191.27mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.3662mL6.8310mL13.6619mL5mM0.2732mL1.3662mL2.7324mL10mM0.1366mL0.6831mL1.3662mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液；该产品在溶液状态不稳定，建议您现⽤现配，即刻使⽤.体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥3.5mg/mL(4.78mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoil1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥3.5mg/mL(4.78mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性MMAF(MonomethylauristatinF)⼀种有效的微管蛋⽩聚合(tubulinpolymerization)抑制剂，⽤作抗肿瘤药物。MMAF(MonomethylauristatinF)⼴泛⽤作抗体偶联药物(ADCs)的细胞毒性成分，如Vorsetuzumabmafodotin和SGN-CD19A。IC50&TargetAuristatin体外研究MMAFinhibitsanaplasticlargecelllymphomaKarpas299,breastcarcinomaH3396,renalcellcarcinoma786-OandCaki-1cellswithIC50sof119,105,257and200nMinvitrocytotoxicityassay[4].体内研究ThemaximumtolerateddoseinmiceofMMAF(MonomethylauristatinF)(>16mg/kg)ismuchhigherthanMMAF(MonomethylauristatinF)(1mg/kg).cAC10-L1-MMAF4hasanMTDof50mg/kginmiceand15mg/kginrats.ThecorrespondingcAC10-L4-MMAF4ADCwasmuchlesstoxic,havingMTDsinmiceandratsof>150mg/kgand90mg/kginrats,respectively[4].PROTOCOLCellAssay[1]Cellsaretreatedwithserialdilutionsoftestmoleculesandincubated4-6daysdependingoncellline.AssessmentofcellulargrowthanddatareductiontogenerateIC50valuesisdoneusingAlamarBluedyereductionassay[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:WhensubcutaneousKarpas299tumorsizereaches300mm3,threeanimalspergroupreceivesoneAdministration[1]injectionof10mgantibodycomponent/kgbodyweightofeithercAC10-L1-MMAF4orcBR96-L1-MMAF4intravenously.Tumorsarethenremovedandplacedinoptimalcuttingtemperaturecompound,and5μm-thinfrozentissuesectionsarestainedusingimmunohistochemistryevaluation[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•JControlRelease.2018May10;277:48-56.•MolTherNucleicAcids.2018Mar2;10:227-236.•TargetOncol.2019Oct;14(5):577-590.•OncolRep.2020Dec9.•UniversityofMinnesota.2022Sep.Seemorecustomervalidationsonwww.MedChemEREFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].DoroninaSO,etal.EnhancedactivityofmonomethylauristatinFthroughmonoclonalantibodydelivery:effectsoflinkertechnologyonefficacyandtoxicity.BioconjugChem.2006Jan-Feb;17(1):114-24.[2].LeeJW,etal.EphA2targetedchemotherapyusinganantibodydrugconjugateinendometrialcarcinoma.ClinCancerRes.2010May1;16(9):2562-70.[3].LeeJJ,etal.Enzymaticprenylationandoximeligationforthesynthesisofstableandhomogeneousprotein-drugconjugatesfortargetedtherapy.AngewChemIntEdEngl.2015Oct5;54(41):12020-4.[4].KimEG,etal.StrategiesandAdvancementinAntibody-DrugConjugateOptimizationforTargetedCancerTherapeutics.McePdfHeightCaution:Produc