Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAvapritinibCat.No.:HY-101561CASNo.:1703793-34-3Synonyms:BLU-285分?式:C??H??FN??分?量:498.56作?靶點:c-Kit;PDGFR作?通路:ProteinTyrosineKinase/RTK儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數據體外實驗DMSO:≥83.33mg/mL(167.14mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.0058mL10.0289mL20.0578mL5mM0.4012mL2.0058mL4.0116mL10mM0.2006mL1.0029mL2.0058mL請根據產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結果的可靠性，澄的儲備液可以根據儲存條件，適當保存；體內實驗的?作液，建議您現?現配，當天使?；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沉淀、析出現象，可以通過加熱和/或超聲的?式助溶)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.01mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.01mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.01mM);ClearsolutionBIOLOGICALACTIVITY?物活性Avapritinib(BLU-285)?種?效、選擇性、?服?活性的KIT和PDGFRA激活環突變激酶抑制劑，其對KITD816V和PDGFRAD842V的IC50值分別為0.27和0.24nM。Avapritinib(BLU-285)與激酶的活性構象結合，并顯?抗腫瘤活性。Avapritinib(BLU-285)減弱ABCB1和ABCG2的傳輸功能。IC50&TargetIC50:0.27nM(KITD816V),0.24nM(PDGFRAD842V)[1]體外研究Avapritinib(BLU-285)hasdemonstratedbiochemicalinvitroactivityontheKITexon17mutantenzyme,KITD816V(IC50=0.27nM).CellularactivityofAvapritinibonKITD816mutantsismeasuredbyautophosphorylationinthehumanmastcellleukemiacelllineHMC1.2,andtheP815mousemastocytomacelllinewithIC50=4and22nM,respectively.InKasumi-1cells,at(8;21)-positiveAMLcelllinewithaKITexon17N822Kmutation,AvapritinibpotentlyinhibitsKITN822Kmutantautophosphorylation(IC50=40nM),downstreamsignaling,aswellascellularproliferation(IC50=75nM)[3].體內研究InvivoAvapritinib(BLU-285)iswelltoleratedandhasdemonstrateddosedependentantitumorefficacy.Completetumorgrowthinhibitionand≥75%KITkinaseinhibitionisobservedwith10mg/kgoncedaily,oraldosingofAvapritinibintheaggressiveKITexon17mutantdrivenP815mastocytomamodelgrownasasolidtumorallograftaswellasinadisseminatedmodelofdisease.Diseaseburden,measuredbywholebodyluciferaseimaging(photons/second/mm2),increases86-foldinthevehiclecontrolanimalsoverthe24daydosingperiodwithwidespreaddiseasedetectableinbothfemurs,thepelvisandcirculatinginperipheralblood.Avapritinibatbothdoses(10or30mg/kgorally,oncedaily)resultsinamarkedreductionofdiseaseburdenthroughoutthestudy.Avapritinibateither10or30mg/kgresultsintumorregressioninallanimalswithdiseaseabrogationindistinguishablefrombackgroundsignalmeasurementsinseveralanimalsbytheendofstudy.Avapritinibisalsowelltoleratedinthisinvivomodelandhasnoadverseeffectsonbodyweightateitherdose[3].PROTOCOLAnimalMice[1]Administration[1]AKasumi-1luc+AMLNOGSCIDmousefemoralinjectionmodelisusedtoassesstheefficacyofAvapritinib(BLU-285)inKITexon17-mutatedCBF-AML.Followinga21daypostinjectionlatencyperiod,micearedosedwithAvapritiniborally,oncedailyat10mg/kgor30mg/kgthroughday45.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE戶使?本產品發表的科研?獻?Biomaterials.16September2022.?MolPharmacol.April5,2022.?MajorinCancerBiology.2019Aug.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WuCP,etal.Avapritinib:ASelectiveInhibitorofKITandPDGFRαthatReversesABCB1andABCG2-MediatedMultidrugResistanceinCancerCellLines.MolPharm.2019Jul1;16(7):3040-3052.[2].EvansEK,etal.AprecisiontherapyagainstcancersdrivenbyKIT/PDGFRAmutations.SciTranslMed.2017Nov1;9(414).pii:eaao1690.[3].EricaEvans,etal.Blu-285,aPotentandSelectiveInhibitorforHematologicMalignancieswithKITExon17Mutations.Blood2015126