Brivanib-alaninate-BMS-582664-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBrivanib(alaninate)Cat.No.:HY-10336CASNo.:649735-63-7Synonyms:BMS-582664分⼦式:C₂₂H₂₄FN₅O₄分⼦量:441.46作⽤靶点:VEGFR;Autophagy作⽤通路:ProteinTyrosineKinase/RTK;Autophagy储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(226.52mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.2652mL11.3261mL22.6521mL5mM0.4530mL2.2652mL4.5304mL10mM0.2265mL1.1326mL2.2652mL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(4.71mM);Suspendedsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(4.71mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.71mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Brivanibalaninate(BMS-582664)⼀种ATP竞争性的VEGFR2抑制剂，IC50值为25nM；可以适度抑制VEGFR1和FGFR1，对VEGFR2的选择性对PDGFRβ的240倍[1]。IC50&TargetVEGFR225nM(IC50)体外研究BrivanibinhibitsVEGFR1andFGFR-1withIC50of0.38μMand0.148μM.BrivanibisnotsensitivetoPDGFRβ,EGFR,LCK,PKCαorJAK-3withIC50allabove1900nM.BrivanibcouldinhibittheproliferationofVEGF-stimulatedHUVECswithIC50of40nM,comparedto276nMinFGF-stimulatedHUVECs.Ontheotherhand,brivanibexhibitslowactivitytotumorcelllines[1].Brivanibdoses≤20µMparadoxicallyenhancesFGF-inducedLX-2cellproliferation,whereashigherbrivanibdoses(≥30µM)inhibitsLX-2cellproliferation.TheinhibitoryeffectofbrivanibonliverfibrosisisnotthroughinhibitionofTGF-β1-inducedstellatecellactivation,andispossiblythroughinhibitionofPDGF-BB-inducedstellatecellactivation[3].体内研究BrivanibdisplaysantitumoractivitiesinH3396xenograftinathymicmice.Atadoseof60and90mg/kg(p.o.),brivanibcompletelyinhibitsthetumorgrowth,withTGIof85%and97%,respectively[1].Moreover,brivanibsignificantlysuppressestumorgrowthinHepatocellularcarcinoma(HCC)xenografts,whichduetothedecreaseinphosphorylationofVEGFR2.Theresultsshowthatthetumorweightsin06-0606xenograftmiceare55%and13%,comparedwiththecontrolsatadoseof50mg/kgand100mg/kg.BrivanibissuggestedtobeefficientintreatmentofHCC[2].Brivanib(50mg/kg,p.o.)attenuatesliverfibrosisandstellatecellactivationinducedbyBDLinmice.BrivanibinhibitsgrowthfactorandgrowthfactorreceptormRNAexpressioninshamcontrolanimalsbutshowsvariableeffectsinbileductligatedanimals[3].PROTOCOLCellAssay[3]ViabilityismeasuredinLX-2cellsusingtheCellCountingKit-8(CCK-8).Using96-wellplateswith2,000cellsperwell,HSCsareincubatedin10%FBS-supplementedDMEMfor24hours,followedbystarvationinserum-freemedia.After24hoursofstarvation,brivanibisaddedatdifferentdoses.Twohourslater,5ng/mLPDGF-BBisadded.Thecellsareincubatedforanadditional72hoursandcellviabilityismeasured.Eachexperimentisperformedinthreereplicatesatleastfourtimes[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMalemice4-6weeksofagearetreated3timesaweekwithatotalof12intraperitoneal(i.p.)injectionsofAdministration[3]150mL/kgTAA.AttheonsetofTAAtreatment,placeboorbrivanib(25or50mg/kg)isadministeredorallyon2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE5consecutivedayswithweekendbreaks.Theanimalsaresacrificed4weeksafterthestartoftheinjections[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•HarvardMedicalSchoolLINCSLIBRARYSeemorecustomervalidationsonwww.MedChemEREFERENCES[1].BhideRS,etal.Discoveryandpreclinicalstudiesof(R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-ol(BMS-540215),aninvivoactivepotentVEGFR-2inhibitor.JMedChem,2006,49(7),2143-2146.[2].HuynhH,etal.Brivanibalaninate,adualinhibitorofvascularendothelialgrowthfactorreceptorandfibroblastgrowthfactorreceptortyrosinekinases,inducesgrowthinhibitioninmousemodelsofhumanhepatocellularcarcinoma.ClinCancerRes,2008,[3].NakamuraI,etal.Correction:BrivanibAttenuatesHepaticFibrosisInVivoandStellateCellActivationInVitrobyInhibitionofFGF,VEGFandPDGFSignalin