Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEVarlitinibCat.No.:HY-10530CASNo.:845272-21-1Synonyms:ASLAN001;ARRY-334543分?式:C??H??ClN?O?S分?量:466.94作?靶點:EGFR作?通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數據體外實驗DMSO:33.33mg/mL(71.38mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.1416mL10.7080mL21.4160mL5mM0.4283mL2.1416mL4.2832mL10mM0.2142mL1.0708mL2.1416mL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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(4.45mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(4.45mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.35mM);ClearsolutionBIOLOGICALACTIVITY?物活性Varlitinib(ASLAN001)有效，可逆的泛EGFR?分?抑制劑，對HER1，HER2和HER4的IC50值分別為7，2，4nM[1]。IC50&TargetHER1HER2HER47nM(IC50)2nM(IC50)4nM(IC50)體外研究Incell-basedassaysusingtumorcellsthatover-expressEGFR(A431)orErbB-2(BT474),Varlitinib(ARRY-334543)potentlyinhibitssubstratephosphorylation.VarlitinibisshowntobehighlyselectiveforEGFR/ErbB-2,anddoesnotshowanysignificantactivitywhenscreenedagainstapanelof104kinases[2].體內研究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.戶使?本產品發表的科研?獻?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].HsiehC,etal.Varlitinibtodemonstrateanti-tumourefficacyinpatient-derivedhepatocellularcarcinomaxenograftmodels.Journalof2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEClinicalOncology34,no.15_suppl[2].MiknisG,etal.ARRY-334543,Apotent,orallyactivesmallmoleculeinhibitorofEGFRandErbB-2.ProcAmerAssocCancerRes,Volume46,2005McePdfHeightCaution:Producthasnotbeen