PF-06447475-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPF-06447475Cat.No.:HY-12477CASNo.:1527473-33-1分?式:C??H??N?O分?量:305.33作?靶點(diǎn):LRRK2作?通路:Autophagy儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:60mg/mL(196.51mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.2751mL16.3757mL32.7515mL5mM0.6550mL3.2751mL6.5503mL10mM0.3275mL1.6376mL3.2751mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥3mg/mL(9.83mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥3mg/mL(9.83mM);ClearsolutionBIOLOGICALACTIVITY?物活性PF-06447475?效，選擇性，能透過(guò)?腦屏障的LRRK2抑制劑，IC50值為3nM。IC50&TargetIC50:3nM(LRRK2)[1].體外研究PF-06447475inhibitsLRRK2enzymeandLRRK2inthewholecellassaywithIC50sof3and25nM,respectively[1].CellsincubatedwithPF-06447475alone(0.5,1,3μM)orinthepresenceofROTsignificantlyreduces(S935)-LRRK2kinasephosphorylationtocontrol.PF-06447475significantlypreservesthenucleusmorphologyandΔΨmofNLCsexposedtoROTcomparedtountreatedandcontrol.PF-475significantlydiminishesROT-inducedROSgenerationtoasimilarextenttocellsexposedtoPF-475alone[2].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Antioxidants(Basel).2022,11(9),1634.?MethodsMolBiol.2021;2322:63-72.Seemorecustomervalidationsonwww.MedChemEREFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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