PF-06447475-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPF-06447475Cat.No.:HY-12477CASNo.:1527473-33-1分⼦式:C₁₇H₁₅N₅O分⼦量:305.33作⽤靶点:LRRK2作⽤通路:Autophagy储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:60mg/mL(196.51mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.2751mL16.3757mL32.7515mL5mM0.6550mL3.2751mL6.5503mL10mM0.3275mL1.6376mL3.2751mL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:≥3mg/mL(9.83mM);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%cornoilSolubility:≥3mg/mL(9.83mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性PF-06447475⾼效，选择性，能透过⾎脑屏障的LRRK2抑制剂，IC50值为3nM。IC50&TargetIC50:3nM(LRRK2)[1].体外研究PF-06447475inhibitsLRRK2enzymeandLRRK2inthewholecellassaywithIC50sof3and25nM,respectively[1].CellsincubatedwithPF-06447475alone(0.5,1,3μM)orinthepresenceofROTsignificantlyreduces(S935)-LRRK2kinasephosphorylationtocontrol.PF-06447475significantlypreservesthenucleusmorphologyandΔΨmofNLCsexposedtoROTcomparedtountreatedandcontrol.PF-475significantlydiminishesROT-inducedROSgenerationtoasimilarextenttocellsexposedtoPF-475alone[2].体内研究InG2019S+ratstreatedwithPF-06447475,asignificantreductioninmicrogliosistolevelsfoundinwild-typeratscouldbeobserved.TheproinflammatorymarkerMHC-IIexpressedonmyeloidcellsbutnotneuronsalsoappearstobelessabundantinconfocalsectionsinG2019S+ratstreatedwithPF-06447475.PF-06447475treatmentinG2019S+ratssignificantlylowersthenumberofCD68cellsrecruitedtotheSNpc.PF-06447475successfullyblockstheenhancedneuroinflammationassociatedwithG2019S-LRRK2expression.TreatmentofG2019S+ratswithPF-06447475preservesTHexpressioninthedorsalstriatum,consistentwithdrugattenuatingneurodegenerationintheSNpc[3].PF-06447475iswelltoleratedinrats[1].PROTOCOLAnimalRats:PF-06447475areadministeredtothedesiredamountinasuspensionsolutionconsistingof10%Administration[3]propyleneglycol,20%PEG-400,and70%0.5%methylcellulose.TodeterminethepotencyofPF-06447475inblockingbrainLRRK2kinaseactivity,wild-typeSprague-Dawleyratsaretreatedat3and30mg/kgPF-06447475(p.o.b.i.d.)for14days,andtotalandphospho-LRRK2aresubsequentlymeasuredfrombraintissuelysates[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•Antioxidants(Basel).2022,11(9),1634.•MethodsMolBiol.2021;2322:63-72.Seemorecustomervalidationsonwww.MedChemEREFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].HendersonJL,etal.Discoveryandpreclinicalprofilingof3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile(PF-06447475),ahighlypotent,selective,brainpenetrant,andinvivoactiveLRRK2kinaseinhibitor.JMedChem.2015Jan8;58(1):419-32.[2].Mendivil-PerezM,etal.NeuroprotectiveEffectoftheLRRK2KinaseInhibitorPF-06447475inHumanNerve-LikeDifferentiatedCellsExposedtoOxidativeStressStimuli:ImplicationsforParkinson'sDisease.NeurochemRes.2016Oct;41(10):2675-2692.[3].DaherJP,etal.Leucine-richRepeatKinase2(LRRK2)PharmacologicalInhibitionAbatesα-SynucleinGene-inducedNeurodegeneration.JBiolChem.2015Aug7;290(32):19433-44.McePdfHeightCautio