Branaplam-LMI070-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBranaplamCat.No.:HY-19620CASNo.:1562338-42-4Synonyms:LMI070;NVS-SM1分⼦式:C₂₂H₂₇N₅O₂分⼦量:393.48作⽤靶点:DNA/RNASynthesis;PotassiumChannel作⽤通路:CellCycle/DNADamage;MembraneTransporter/IonChannel储存⽅式:4°C,sealedstorage,awayfrommoistureandlight*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoistureandlight)溶解性数据体外实验DMSO:5mg/mL(12.71mM;ultrasonicandwarmingandheatto80°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.5414mL12.7071mL25.4143mL5mM0.5083mL2.5414mL5.0829mL10mM0.2541mL1.2707mL2.5414mL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(sealedstorage,awayfrommoistureandlight)。-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：1%DMSO>>99%salineSolubility:0.12mg/mL(0.30mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1mg/mL(2.54mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥0.71mg/mL(1.80mM);Clearsolution4.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥0.71mg/mL(1.80mM);Clearsolution5.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥0.57mg/mL(1.45mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Branaplam(LMI070;NVS-SM1)⼀种⼝服有效和选择性的SMN2拼接调节剂，对SMN的EC50为20nM。Branaplam抑制hERG，IC50为6.3μM。Branaplam在严重的脊髓性肌萎缩症(SMA)⼩⿏模型中可提⾼全长SMN蛋⽩并延长其⽣存期。IC50&TargetIC50:20nM(SMN)[1]EC50:6.3μM(hERG)[2]体外研究Branaplam(LMI070;NVS-SM1)treatmentinduceschangesinthelevelsof175genesinhumanfibroblasts[1].体内研究Branaplam(LMI070;NVS-SM1;3,10,30mg/kg;oral)producesdose-dependentelevationsofSMN2-FLtranscriptandSMNproteininbrainandspinalcord[1].Branaplam(1mg/kgofIV;3mg/kgofPO)hasaCLof25mL/min/kgandanAUCof3.03μM•h[2].AsingleBranaplam(oral;30mg/kg)resultsinsignificantanddurableSMNproteinelevationinbrainforupto160hoursinC/+mice[1].Branaplam(oral;0.03,0.1,0.3,1,3mg/kg)improvesbodyweightandextendeslifespaninnSMNΔ7mice[1].AnimalModel:C/+SMAmousemodel[1]Dosage:3,10,30mg/kgAdministration:OralResult:Produceddose-dependentelevationsofSMN2-FLtranscriptandSMNproteininbrainandspinalcord.AnimalModel:MaleSprague-Dawleyrat[2]Dosage:1mg/kg(IV);3mg/kg(PO)(PharmacokineticAnalysis)Administration:IVorPO2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:HadaCLof25mL/min/kgandanAUCof3.03μM•h.户使⽤本产品发表的科研⽂献•Nature.2021Aug;596(7871):291-295.•NucleicAcidsRes.2021Sep7;49(15):8462-8470.•bioRxiv.2020Jun.•bioRxiv.2020Feb.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].PalacinoJ,etal.SMN2splicemodulatorsenhanceU1-pre-mRNAassociationandrescueSMAmice.NatChemBiol.2015Jul;11(7):511-517.[2].CheungAK,etal.DiscoveryofSmallMoleculeSplicingModulatorsofSurvivalMotorNeuron-2(SMN2)fortheTreatmentofSpinalMuscularAtrophy(SMA).JMedChem.2018Dec27;61(24):11021-11036.McePdfHeightCaution:Producthasnotbee