Varlitinib-ASLAN001-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEVarlitinibCat.No.:HY-10530CASNo.:845272-21-1Synonyms:ASLAN001;ARRY-334543分⼦式:C₂₂H₁₉ClN₆O₂S分⼦量:466.94作⽤靶点:EGFR作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:33.33mg/mL(71.38mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1416mL10.7080mL21.4160mL5mM0.4283mL2.1416mL4.2832mL10mM0.2142mL1.0708mL2.1416mL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.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.08mg/mL(4.45mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(4.45mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.35mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Varlitinib(ASLAN001)有效，可逆的泛EGFR⼩分⼦抑制剂，对HER1，HER2和HER4的IC50值分别为7，2，4nM[1]。IC50&TargetHER1HER2HER47nM(IC50)2nM(IC50)4nM(IC50)体外研究Incell-basedassaysusingtumorcellsthatover-expressEGFR(A431)orErbB-2(BT474),Varlitinib(ARRY-334543)potentlyinhibitssubstratephosphorylation.VarlitinibisshowntobehighlyselectiveforEGFR/ErbB-2,anddoesnotshowanysignificantactivitywhenscreenedagainstapanelof104kinases[2].体内研究Varlitinibtreatmentpotentlyinhibitstumorgrowthwithcompletetumorregressionobservedatdosingof100mg/kgtwiceaday.AfterfivedaysofVarlitinibtreatment,phosphorylationofHER1-3,RAS/RAF/MEK/MAPK,p70S6K,S6ribosomal,4EBP1,Cdk-2,Cdc-2andretinoblastomaarestronglyinhibited.VarlitinibtreatmentresultsinasignificantreductioninsurvivinandaconcomittantincreaseinCaspase3cleavageproducts[1].Inmurinexenograftmodels,Varlitinib(ARRY-334543)demonstratessignificantdose-related(25,50,100mg/kg)tumorgrowthinhibitioninA431-derivedtumorswhenadministeredorally,twiceaday,for21days[2].PROTOCOLAnimalMice:TheeffectsofVarlitinibistestedinpatient-derivedHCCxenograftinSCIDmice(HCC29-0909A)withAdministration[1]co-expressionofHER1,HER2andHER3recepors.MicearetreatedwithVarlitinibwhenthetumorsreachthesizeofapproximately100-150mm3.Tumorsizemeasurementsareperformedtwiceaweekandtumorvolumesarecalculated[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].HsiehC,etal.Varlitinibtodemonstrateanti-tumourefficacyinpatient-derivedhepatocellularcarcinomaxenograftmodels.Journalof2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEClinicalOncology34,no.15_suppl[2].MiknisG,etal.ARRY-334543,Apotent,orallyactivesmallmoleculeinhibitorofEGFRandErbB-2.ProcAmerAssocCancerRes,Volume46,2005McePdfHeightCaution:Producthasnotbeen