Fruquintinib-HMPL-013-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEFruquintinibCat.No.:HY-19912CASNo.:1194506-26-7Synonyms:HMPL-013分⼦式:C₂₁H₁₉N₃O₅分⼦量:393.39作⽤靶点:VEGFR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:5.88mg/mL(14.95mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.5420mL12.7100mL25.4201mL5mM0.5084mL2.5420mL5.0840mL10mM0.2542mL1.2710mL2.5420mL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:≥0.59mg/mL(1.50mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥0.59mg/mL(1.50mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥0.59mg/mL(1.50mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Fruquintinib(HMPL-013)有效，选择性的VEGFR1/2/3抑制剂，IC50值分别为33，0.5，and35nM。IC50&TargetVEGFR1VEGFR2VEGFR333nM(IC50)35nM(IC50)0.5nM(IC50)体外研究FruquintinibdemonstratespotentinhibitiononVEGF-AdependentKDRphosphorylationinHEK293-KDRcellsandVEGF-AinducedproliferationinprimaryHUVECswithIC50sof0.6±0.2nMand1.7nM,respectively.Similarly,potentVEGFR3attenuationbyfruquintinibisobservedinprimaryHLECs,withIC50sof1.5nMand4.2nMforVEGF-CstimulatedVEGFR3phosphorylationandproliferation,respectively.Fruquintinibsuppressesthetubebranching,tubelengthandareainaconcentration-dependentmanner.ThetubulelengthofprimaryHUVECsdecreasedby74%and94%at0.03and0.3μMoffruquintinib,respectively.FruquintinibinhibitsHUVECtubulegrowthandCAMangiogenesis.Tubeformationissuppressedsignificantlyaftertreatmentwithfruquintinibat0.3μMfor18hours[1].体内研究GastriccancerBGC-823modelisfoundtobemostsensitivetofruquintinib.Inthismodel,fruquintinibinhibitstumorgrowthby62.3%and95.4-98.6%,at0.5and2mg/kgoncedailydosing,respectively.Whenthedoseiselevatedto5mg/kgand20mg/kg,thetumorsregressby24.1%and48.6%,respectively.Thelevelofanti-tumorgrowthactivityoffruquintinibvariesindifferenttumorxenograftmodels.Fruquintinibsignificantlydecreasesthemicro-vesseldensityevenatthelowestdoseof0.8mg/kg[1].PROTOCOLCellAssay[1]PrimaryHUVECsorHLECsinexponentialphasearesuspendedin100μLofRPMI-1640mediacontaining0.5%FBS,andseededat5000cell/wellin96-wellplatespre-coatedwith0.2%gelatinorfibronectin,andincubatedovernightina5%CO2,37°Cincubator.FruquintinibandVEGF-A165orVEGF-C(50ng/mL)areaddedandincubatedfor48hours.ViabilityofthecellsisdeterminedusingCCK-8assayformat[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:ThepatientderivedxenograftmodelsareestablishedaftertheprimarytumoradoptedserialpassagesAdministration[1]invivo.Oncetumorshavegrownto100-300mm3,theanimalsarerandomlyassignedwith6-8animalspergroup.Themicearetreatedorallywiththevehicle(controlgroup)orfruquintinibatadoserangeof0.5-20mg/kgsuspendedinthevehicle(treatedgroup)oncedailyfor3weeks.Incombinationstudies,docetaxel(Taxotere,5mg/kg)oroxaliplatin(10mg/kg)isadministeredtonudemouseviaintravenousinjection,onceaweek.Tumorsizeandbodyweightsaremeasured3timesaweek.Tumorvolumes(TV)arecalculated[1].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CellReprogram.2021Jun2.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].SunQ,etal.Discoveryoffruquintinib,apotentandhighlyselectivesmallmoleculeinhibitorofVEGFR1,2,3tyrosinekinasesforcancertherapy.CancerBiolTher.2014;15(12):1635