Avapritinib-BLU-285-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAvapritinibCat.No.:HY-101561CASNo.:1703793-34-3Synonyms:BLU-285分⼦式:C₂₆H₂₇FN₁₀分⼦量:498.56作⽤靶点:c-Kit;PDGFR作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥83.33mg/mL(167.14mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0058mL10.0289mL20.0578mL5mM0.4012mL2.0058mL4.0116mL10mM0.2006mL1.0029mL2.0058mL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。-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(5.01mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.01mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.01mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Avapritinib(BLU-285)⼀种⾼效、选择性、⼝服⽣活性的KIT和PDGFRA激活环突变激酶抑制剂，其对KITD816V和PDGFRAD842V的IC50值分别为0.27和0.24nM。Avapritinib(BLU-285)与激酶的活性构象结合，并显⽰抗肿瘤活性。Avapritinib(BLU-285)减弱ABCB1和ABCG2的传输功能。IC50&TargetIC50:0.27nM(KITD816V),0.24nM(PDGFRAD842V)[1]体外研究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].体内研究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—您⾝边的抑制剂⼤师www.MedChemE户使⽤本产品发表的科研⽂献•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