NLX-204-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemENLX-204hydrochlorideCat.No.:HY-124631A分⼦式:C₂₀H₂₃Cl₂F₂N₃O₂分⼦量:446.32作⽤靶点:5-HTReceptor作⽤通路:GPCR/GProtein;NeuronalSignaling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(224.05mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.2405mL11.2027mL22.4054mL5mM0.4481mL2.2405mL4.4811mL10mM0.2241mL1.1203mL2.2405mL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:≥2.5mg/mL(5.60mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.60mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性NLX-204(hydrochloride)⼀种具有⼝服活性、有效、⾼亲和⼒和选择性的5-HT1A受体偏向激动剂(pKi=10.19)。NLX-204(hydrochloride)对α1和D2受体的亲和⼒⾼于对其他脱靶受体的亲和⼒。NLX-204(hydrochloride)可⽤于抗抑郁的研究[1]。IC50&Target5-HT1AReceptor10.19(pKi)体外研究NLX-204(10μM)(hydrochloride)showssubstantialbindinginhibition(higherthan50%)foradrenergicα1Aandα2AanddopaminergicD2Sreceptors.NLX-204(1μM)(hydrochloride)exhibitsmuchlowerbindinginhibitionatD2andα2Areceptorsbutmaintainsarelativelyhighvaluefortheα1Areceptor.NLX-204(0.1~10μM)(hydrochloride)hasalowpropensityforhERGchannelblockadeandsuggeststhattheinvestigatedserieshasalowriskwithrespecttohERG-relatedcardiacsafety.NLX-204(hydrochloride)alsoexhibitshighmicrosomalstability.NLX-204(hydrochloride)displaysnoP-gpinhibition(6.5%ofinhibitionat10μM)aswellasnegligibleinhibitionofCYP3A4andCYP2D6(23.2and15.9%at10μM,respectively).NLX-204(hydrochloride)doesnotelicitflatbodyposture(FBP),acommonsideeffectofthe5-HT1Areceptorstimulation,suggestingthatitspreferenceforactivationof5-HT1Areceptor-mediatedERK1/2phosphorylationinvitrotranslatestopreferentialantidepressanteffectsratherthaninductionof"behavioralsyndrome"[1].体内研究NLX-204(2.5mg/kg;p.o.)(hydrochloride)israpidlyabsorbedfromthegastrointestinaltract(Tmax=15min),reachesrelativelyhighserumconcentrationsandshowshigherconcentrationthanthoseinserumforalldoses[1].NLX-204(0.04~2.5mg/kg;p.o.)(hydrochloride)showsthatstatisticallysignificantelevationofpERK1/2isobservedatthetwohighestdoses(2.5and0.63mg/kg),butatendencytoincreasepERK1/2levelsisalsoseenatlowerdoses[1].NLX-204(hydrochloride)robustlyandsignificantlyincreasesratPFCERK1/2phosphorylationinatimedependentmanner[1].AnimalModel:MaleWistarrats(170~200g)[1]Dosage:2.5mg/kgAdministration:P.o.Result:Rapidlyabsorbedfromthegastrointestinaltract(Tmax=15min)andreachedrelativelyhighserumconcentrations.AnimalModel:MaleWistarrats(170~200g)[1]Dosage:2.5mg/kg(PharmacokineticAnalysis)Administration:P.o.Result:TheconcentrationofNLX-204inbraintissuewashigherthanthoseinserumforall2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEdoses.AnimalModel:MaleWistarrats(170~200g)[1]Dosage:0.04~2.5mg/kgAdministration:P.o.Result:StatisticallysignificantelevationofpERK1/2wasobservedatthetwohighestdoses(2.5and0.63mg/kg),butatendencytoincreasepERK1/2levelswasalsoseenatlowerdoses.REFERENCES[1].SniecikowskaJ,etal.NovelAryloxyethylDerivativesof1-(1-Benzoylpiperidin-4-yl)methanamineastheExtracellularRegulatedKinases1/2(ERK1/2)Phosphorylation-PreferringSerotonin5-HT1AReceptor-BiasedAgonistswithRobustAntidepressant-likeActivity.JMedChem.2019;62(5):2750-2771.McePdfH