Luminespib-VER-52296-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemELuminespibCat.No.:HY-10215CASNo.:747412-49-3Synonyms:VER-52296;AUY922;NVP-AUY922分⼦式:C₂₆H₃₁N₃O₅分⼦量:465.54作⽤靶点:HSP;Autophagy;Apoptosis作⽤通路:CellCycle/DNADamage;MetabolicEnzyme/Protease;Autophagy;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥62mg/mL(133.18mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1480mL10.7402mL21.4804mL5mM0.4296mL2.1480mL4.2961mL10mM0.2148mL1.0740mL2.1480mL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1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE、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%salineSolubility:≥2.5mg/mL(5.37mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.37mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.37mM);Clearsolution4.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(5.37mM);Clearsolution5.请依序添加每种溶剂：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.37mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Luminespib(VER-52296)有效的HSP90抑制剂，抑制HSP90α和HSP90β的IC50分别为7.8和21nM[1]。IC50&TargetHSP90αHSP90βGRP94TRAP-17.8nM(IC50)21nM(IC50)535nM(IC50)85nM(IC50)体外研究LuminespibisapotentandselectiveHSP90inhibitor,withIC50sandKisof21±16,8.2±0.7nMagainstHSP90βandof7.8±1.8,9.0±5.0nMforHSP90α.LuminespibshowsweakactivityagainstGRP94andTRAP-1wichIC50sof535±51nM(Ki,108nM)and85±8nM(Ki,53nM),respectively.Luminespibexhibitsinhibitoryeffectonproliferationofvarioushumantumorcelllines(2.3-49.6nM),inducescellcyclearrestandapoptosisanddepletesclientproteinsinhumancancercells(80nM)[1].Luminespib(100nM)significantlyreducesCD40Lfibroblast-inducedchangesinimmunophenotypeandSTAT3signalingbutwithnoeffectontheviabilityofchroniclymphocyticleukemia(CLL)cells.Luminespib(500nM)incombinationwithNSC118218moreeffectivelyinducesapoptosisincellsinco-culturethaneitherdrugalone,andovercomesfibroblast-derivedresistancetoHsp90inhibitor[2].LuminespibshowsgreatinhibitionofpancreaticcancercellswithIC50ofat10nM.Luminespib(10nM)reducestheexpressionandtheepidermalgrowthfactor(EGF)-mediatedactivationofEGFRandsubstantiallydisruptsEGFsignalingintermsofdiminishingdownstreamphosphorylationofERKThr202/Tyr204.Luminespib(10nM)significantlyblockspancreaticcancercellmigrationandinvasionbothintheabsenceandpresenceofEGF[3].体内研究Luminespib(50,75mg/kg,i.p.)significantlyinhibitstumorgrowthrate,reducingthemeanweightsoftumorsonday11inhumantumorxenografts[2].Luminespib(50mg/kg/week,3×25mg/kg/week)significantlyreducestumorgrowthratesandlowerstumorweightsintheL3.6plpancreaticcancercell-bearingmicemodel[3].PROTOCOLCellAssay[1]CelllinesaregrowninDMEM/10%FCS,2mMglutamine,andnonessentialaminoacidsinahumidified2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEatmosphereof5%CO2inair.AlllinesarefreeofMycoplasma.CellproliferationisdeterminedusingtheSRBassayfortumorcellsandprostateepithelialcells,theWST-1assayforMCF10AandHB119,oranalkalinephosphataseassayforHUVECandHDMEC.GI50isthecompoundconcentrationinhibitingcellproliferationby50%comparedwithvehiclecontrols.Activecaspase-3/7ismeasuredusingahomogenouscaspaseassaykit[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]Forefficacystudies,humantumorxenograftsareestablisheds.c.inathymicmice.WM266.4cellsarealsoinjectedi.v.togenerateexperimentallungmetastasesandPC3LN3prostatecarcinomacellsareimplantedintotheprostatesofmalemice.Dosingbyi.p.withLuminespibcommenceswhentumorsarewellestablished.Tumorgrowthismonitoredandatstudyendsamplesareharvestedforanalysis[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•Blood.2018Jul19;132(3):307-320.•NatCommun.2017Sep4;8(1):422.•ClinCancerRes.2018Feb15;24(4):794-806.•Leukemia.2019Jun;33(6):1373-1386.•JBiomedSci.2021Jul23;28(1):55.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].Eccles,SuzanneA.,etal.NVP-AUY922:ANovelHeatShockProtein90InhibitorActiveagainstXenograftTumorGrowth,Angiogenesis,andMetastasis.CancerResearch(2008),68(8),2850-2860.[2].BestOG,etal.Heatshockprotein-90inhibitor,NVP-AUY922,iseffectiveincombinationwithNSC118218againstchroniclymphocyticleukemiacellsculturedonCD40L-stromallayerandinhibitstheiractivated/proliferativephenotype.LeukLymphoma.2012J[3].MoserC,etal.StoeltzingO.TargetingHSP90bythenovelinhibitorNVP-AUY922reducesgrowthandangiogene