M3258-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEM3258Cat.No.:HY-111790CASNo.:2285330-15-4分⼦式:C₁₇H₂₀BNO₅分⼦量:329.16作⽤靶点:Proteasome;Apoptosis作⽤通路:MetabolicEnzyme/Protease;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:250mg/mL(759.51mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.0380mL15.1902mL30.3804mL5mM0.6076mL3.0380mL6.0761mL10mM0.3038mL1.5190mL3.0380mL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%salineSolubility:≥2.08mg/mL(6.32mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(6.32mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(6.32mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性M3258⼀种⼝服⽣物利⽤度⾼、有效、可逆、⾼选择性的免疫蛋⽩酶体亚单位LMP7(β5i)抑制剂。M3258对LMP7的IC50为3.6nM，在细胞中IC50为3.4nM。M3258在多发性⾻髓瘤异种移植模型中显⽰出很强的抗肿瘤作⽤。在多发性⾻髓瘤细胞中，M3258导致肿瘤LMP7活性和泛素化蛋⽩转换的显著且持久的抑制以及诱导凋亡(apoptosis)。IC50&TargetLMP7[1]体外研究M3258inhibitshumanLMP7withameanIC50of4.1nM.M3258displaysweakactivityagainsttheconstitutiveproteasomesubunitβ5(meanIC50=2519nM).M3258potentlyinhibitsLMP7inthehumanmultiplemyelomacelllinesMM.1SandU266B1andinhuman,rat,anddogPBMCswithIC50sbetween2and37nM[2].M3258inducesa>fourfoldaccumulationofubiquitinatedproteinswithanEC50of1980nMinMM.1Scells.M3258interfereswithimmunoproteasomefunction.M3258alsoinducesapoptosisassessedbycaspase3/7activity(EC50=420nM;>3.5-foldinduction)andreducesMM.1Scellviability(IC50=367nM)[2].CellViabilityAssay[2]CellLine:MM.1ScellsConcentration:0.01-100nMIncubationTime:2hoursResult:PotentlyinhibitedLMP7inthehumanmultiplemyelomacelllinesMM.1S(IC50=2.2nM).体内研究M3258(1mg/kg;10mg/kg)showssuperiorantitumorefficacyinselectedmultiplemyelomaandmantlecelllymphomaxenograftmodelscomparedwiththeapprovednonselectiveproteasomeinhibitorsbortezomibandixazomib[2].AnimalModel:FemaleH2dRag2miceorfemaleCB-17SCIDmice(U266B1subcutaneousxenograftmodel;MM.1Ssubcutaneousxenograftmodel)[2]Dosage:1mg/kginU266B1subcutaneousxenograftmodel;10mg/kginMM.1SsubcutaneousxenograftmodelAdministration:P.o.;eitheroncedaily,every2daysortwiceweekly(days1and4)Result:Displayedsignificantandstrongantitumorefficacy.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE户使⽤本产品发表的科研⽂献•CellDeathDis.2022Oct8;13(10):860.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].KleinM,etal.Structure-BasedOptimizationandDiscoveryofM3258,aSpecificInhibitoroftheImmunoproteasomeSubunitLMP7(β5i)[publishedonlineaheadofprint,2021Jul6].JMedChem.2021;10.1021/acs.jmedchem.1c00604.[2].SandersonMP,etal.M3258IsaSelectiveInhibitoroftheImmunoproteasomeSubunitLMP7(β5i)DeliveringEfficacyinMultipleMyelomaModels[publishedonlineaheadofprint,2021May27].MolCancerTher.2021;10.1158/1535-7163.MCT-21-0005.McePdfHeightCaution:Producthasnot