Avitinib-maleate-Abivertinib-maleate-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAvitinibmaleateCat.No.:HY-19816ACASNo.:1557268-88-8Synonyms:Abivertinibmaleate;AC0010maleate分?式:C??H??FN?O?分?量:603.6作?靶點(diǎn):EGFR作?通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK儲(chǔ)存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥100mg/mL(165.67mM)H2O:<0.1mg/mL(ultrasonic;warming;heatto60°C)(insoluble)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.6567mL8.2836mL16.5673mL5mM0.3313mL1.6567mL3.3135mL10mM0.1657mL0.8284mL1.6567mL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(sealedstorage,awayfrommoisture)。-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)1/3MasterofBioactiveMolecules—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(4.14mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.14mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.14mM);ClearsolutionBIOLOGICALACTIVITY?物活性Avitinib(Abivertinib)maleate?種于吡咯并嘧啶的不可逆的表??長(zhǎng)因?受體(EGFR)抑制劑，IC50值為7.68nM。IC50&TargetEGFR7.68nM(IC50)體外研究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].體內(nèi)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?邊的抑制劑?師www.MedChemElevelsof12.5mg/kgand50mg/kgfor17dayswhenTVvalueinvehiclecontrolgroupreachedapproximately2000mm3.After17-daydosing,animalsinthevehiclecontrolgrouparesacrificed,whereasanimalsinavitinibgroupsarecontinuallydailyadministratedwithincreaseddoseat500mg/kgtillthetestmicecannottoleratethetreatment.MousebodyweightandTVaremeasuredtwiceperweek.TVisthenusedforthecalculationoftumorinhibitoryrateandtumorregressionrate[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶(hù)使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Molecules.2021May5;26(9):2717.?JPharmBiomedAnal.2019Feb5;164:659-667.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].XuX,etal.AC0010,anIrreversibleEGFRInhibitorSelectivelyTargetingMutatedEGFRandOvercomingT790M-InducedResistanceinAnimalModelsandLungCancerPatients.MolCancerTher.20