Avitinib-maleate-Abivertinib-maleate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAvitinibmaleateCat.No.:HY-19816ACASNo.:1557268-88-8Synonyms:Abivertinibmaleate;AC0010maleate分⼦式:C₃₀H₃₀FN₇O₆分⼦量:603.6作⽤靶点:EGFR作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:≥100mg/mL(165.67mM)H2O:<0.1mg/mL(ultrasonic;warming;heatto60°C)(insoluble)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM1.6567mL8.2836mL16.5673mL5mM0.3313mL1.6567mL3.3135mL10mM0.1657mL0.8284mL1.6567mL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；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(4.14mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.14mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.14mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Avitinib(Abivertinib)maleate⼀种于吡咯并嘧啶的不可逆的表⽪⽣长因⼦受体(EGFR)抑制剂，IC50值为7.68nM。IC50&TargetEGFR7.68nM(IC50)体外研究Avitinibisstructurallydistinctfrompreviouslyreportedpyrimidine-basedirreversibleEGFRinhibitorssuchasosimertinibandrociletinib.AvitinibisdesignedspecificallytoinhibitEGFRactivemutationsandtheT790Macquiredresistantmutation,whilesparingwildtypeEGFR.AvitinibselectivelyinhibitsEGFRactiveandT790Mmutationswithupto298-foldincreaseinpotencycomparedtowild-typeEGFR.AvitinibexhibitspotentinhibitoryactivitywithIC50valueof0.18nMagainstEGFRL858R/T790Mdoublemutations,nearly43-foldgreaterpotencyoverwild-typeEGFR(IC50=7.68nM).AvitinibselectivelyinhibitsmutantEGFRphosphorylationwithIC50valuesof7.3nMand2.8nMinNCI-H1975andNIH/3T3_TC32T8cells,about115-and298-foldmoresensitivethanthatoftheinhibitionofwildtypeEGFRinA431[1].体内研究Oraladministrationofavitinibatdailydoseof500mg/kgresultsincompleteremissionoftumorswithEGFRactiveandT790Mmutationsforover143dayswithnoweightloss.Threemajormetabolitesofavitinibaretestedandshownowild-typeEGFRinhibitionandoff-targeteffectssuchasinhibitionofIGF-1R.Avitinibissafeinnon-smallcelllungcancer(NSCLC)patientsatthedoserangebetween50mgand550mgonceperdayandnohyperglycemiaandothersevereadverseeffectsaredetectedsuchasgrade3QTprolongation[1].PROTOCOLCellAssay[1]Cellproliferationisassayedbyacellviabilityreagent,WST-1.Cellsareseededatoptimaldensityonto96-wellplatesandincubatedfor24hours,followedbyavitinibtreatmentfor72hours.CellviabilityisthenassayedbyincubatingcellswithWST-1reagentfor2-3hrs[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalRats:Toassessthepotentialskintoxicityofavitinib,aratmodelisused.RatsareadministrateddailywithAdministration[1]avitinibat300mg/kgfor4weeks,andincontrolgroupsgefitinibat50mg/kgorvehiclecontrol(0.5%MC)isadministrated[1].Mice:NCI-H1975tumorbearingmiceareorallytreatedwithavehiclecontrol(0.5%MC),avitinibatdose2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemElevelsof12.5mg/kgand50mg/kgfor17dayswhenTVvalueinvehiclecontrolgroupreachedapproximately2000mm3.After17-daydosing,animalsinthevehiclecontrolgrouparesacrificed,whereasanimalsinavitinibgroupsarecontinuallydailyadministratedwithincreaseddoseat500mg/kgtillthetestmicecannottoleratethetreatment.MousebodyweightandTVaremeasuredtwiceperweek.TVisthenusedforthecalculationoftumorinhibitoryrateandtumorregressionrate[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•Molecules.2021May5;26(9):2717.•JPharmBiomedAnal.2019Feb5;164:659-667.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].XuX,etal.AC0010,anIrreversibleEGFRInhibitorSelectivelyTargetingMutatedEGFRandOvercomingT790M-InducedResistanceinAnimalModelsandLungCancerPatients.MolCancerTher.20