PLX5622-hemifumarate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPLX5622hemifumarateCat.No.:HY-114153A分⼦式:C₂₃H₂₁F₂N₅O₃分⼦量:453.45作⽤靶点:c-Fms作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:100mg/mL(220.53mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.2053mL11.0266mL22.0531mL5mM0.4411mL2.2053mL4.4106mL10mM0.2205mL1.1027mL2.2053mL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,awayfrommoisture)。-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:≥3.25mg/mL(7.17mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥3.25mg/mL(7.17mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoil1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥3.25mg/mL(7.17mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性PLX5622hemifumarate⾼度选择性的、能透过⾎脑屏障的、⼝服有效的CSF1R抑制剂，IC50值为0.016µM，Ki值为5.9nM，可⽤于病程发展前和过程中，扩⼤的和特异性的⼩胶质细胞的消除。PLX5622hemifumarate具有较好的药理学特性。IC50&TargetCSF1R[1]体外研究PLX5622(1-20μM;3days)hemifumarateeffectivelydepletesmicrogliawithoutaffectingoligodendrocytesorastrocytesincerebellarslices.PLX5622(4μM;3days)hemifumaratecausesa30-40%reductioninNG2+orPDGFRα+cells,andthisincreasedto90-95%at20μM.NoreductionofNG2+orPDGFRα+OPCsisobservedinslicesexposedto1μMor2μMPLX5622despiterobust(~95%)depletionofthemicroglialcells[3].体内研究PharmacodynamicsofPLX5622hemifumarateinpreclinicalstudiesPLX5622(1200ppm;chow;for3weeksor3days;adultC57/Bl6wildtypemice)hemifumarateleadstoaround80%ofmicroglialostafter3daysoftreatmentanda99%microglialossafter3weeksoftreatment.PLX5622(adultC57/Bl6wildtypemiceaged3months;dietfor3weeks)decreasesmicrogliaincortex,striatum,cerebellumandhippocampus[4].PLX5622(50ꢀmg/kg;intraperitonealinjection;once(neonatalrat)ortwice(adultrat)aday;foratotalof14days)hemifumaratedepletesmicrogliaby80-90%within3daysoftreatment,whichincreasesto>90%by7days.After14daysofPLX5622treatment,microgliaisdepletedby>96%inbothneonatesandadultswhilepreservingbaselineastrocytequantity.(Asingledailyinjectionof0.65%PLX5622suspendedin5%dimethylsulfoxideand20%KolliphorRH40in0.01ꢀMPBSissufficientforneonatalmicrogliadepletion,adultdepletionrequiresinjectionstwicedaily)[5].PLX5622(formulatedinAIN-76Astandardchowat1200mg/kg;for28days)hemifumarateleadstoreductioninmicrogliathroughouttheCNSin14-month-old5xfADmice[6].PharmacokineticsofPLX5622hemifumarateinpreclinicalspecies[4]SpeciesIVPO(gavage)Dose(mg/kg)AUC0-∞(ng•hr/mL)CL(mL/min/kg)Vss(L/kg)t1/2(hr)Dose(mg/kg)AUC0-∞(ng•hr/mL)Cmax(ng/mL)FMouse1.9215,5002.10.342.645215,00026,30059%Rat(male)1.132,6304599,60012,00095%Rat(female)1.135,1103.71.03.945181,00015,60089%Dog1.006,2303.02.3154596,5003,63034%Monkey1.352,100111.62.2NDNDNDNDPreparationofgavagedosingsuspensionsforPLX5622hemifumarate[4]PLX5622hemifumarateisdissolvedinDMSOataconcentrationthatis20xthefinaldosingsolution.Thecompoundstockisprotectedfromlight.Afreshstockismadeeachweek.Thecomponentsofthediluentgenerallyarepreparedadayormoreinadvancebecausetheytaketimetodissolvecompletely:a)2%hydroxypropylmethylcellulose(HPMC):2.0gpowderwasbroughtto100mLdeionizedwater;b)25%Polysorbate80(PS80):25gwasbroughtto100mLdeionizedwater.Tomake100mLdiluent,add25mLof2%HPMCstock(0.5%final)and4mLof25%PS80stock(1%final)to71mLdeionizedwatertohavefinal100mL.Finalcompositionaftermixingwithcompound:0.5%HPMC,1%PS80,2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE5%DMSO.Oneachdosingday,thecompoundstockisdiluted20-foldasfollows:19volumesofdiluentaremeasuredintothetube,and1volumeofthe20xcompound/DMSOstockisadded.Thecapisclosedandthecontentofthetubeismixedbyinversionandplacedinasonicatingwaterbathtomakeauniformsuspension.户使⽤本产品发表的科研⽂献•Nature.2021Feb;590(7847):612-617.•BrainBehavImmun.2022Oct3;S0889-1591(22)00398-1.•BasicResCardiol.2022Oct24;117(1):52.•CellRep.2020Aug11;32(6):108041.•Elife.2021Jun23;10:e67772.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].SpangenbergE,etal.SustainedmicroglialdepletionwithCSF1RinhibitorimpairsparenchymalplaquedevelopmentinanAlzheimer'sdiseasemodel.NatCommun.2019Aug21;10(1):3758.[2].LeeS,etal.Targetingmacrophageandmicrogliaactivationwithcolonystimulatingfactor1receptorinhibitorisaneffectivestrategytotreatinjury-triggeredneuropathicpain.MolPain.2018Jan-Dec;14:1744806918764979.[3].LiuY,etal.Concentration-dependenteffectsofCSF1Rinhibitorsonoligodendrocyteprogenitorcellsexvivoandinvivo.ExpNeurol.2019;318:32-41.[4].BadimonA,etal.Negativefeedbackcontrolofneuronalactivitybymicroglia.Nature.2020;586(7829):417-423.[5].Andrew