Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBrivanib(alaninate)Cat.No.:HY-10336CASNo.:649735-63-7Synonyms:BMS-582664分?式:C??H??FN?O?分?量:441.46作?靶點:VEGFR;Autophagy作?通路:ProteinTyrosineKinase/RTK;Autophagy儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:100mg/mL(226.52mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.2652mL11.3261mL22.6521mL5mM0.4530mL2.2652mL4.5304mL10mM0.2265mL1.1326mL2.2652mL請根據(jù)產(chǎn)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(fù)凍融造成的產(chǎn)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(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?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(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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(xiàn)沉淀、析出現(xiàn)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(4.71mM);Suspendedsolution;Needultrasonic2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(4.71mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.71mM);ClearsolutionBIOLOGICALACTIVITY?物活性Brivanibalaninate(BMS-582664)?種ATP競爭性的VEGFR2抑制劑，IC50值為25nM；可以適度抑制VEGFR1和FGFR1，對VEGFR2的選擇性對PDGFRβ的240倍[1]。IC50&TargetVEGFR225nM(IC50)體外研究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].體內(nèi)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?邊的抑制劑?師www.MedChemE5consecutivedayswithweekendbreaks.Theanimalsaresacrificed4weeksafterthestartoftheinjections[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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