AZD7325-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAZD7325Cat.No.:HY-111052CASNo.:942437-37-8分?式:C??H??FN?O?分?量:354.38作?靶點(diǎn):GABAReceptor;CytochromeP450作?通路:MembraneTransporter/IonChannel;NeuronalSignaling;MetabolicEnzyme/Protease儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:250mg/mL(705.46mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.8218mL14.1091mL28.2183mL5mM0.5644mL2.8218mL5.6437mL10mM0.2822mL1.4109mL2.8218mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請?jiān)?個?內(nèi)使?，-20°C儲存時，請?jiān)?個?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，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?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(5.87mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(5.87mM);ClearsolutionBIOLOGICALACTIVITY?物活性AZD7325具有?服活性的α2,3receptor的正向別構(gòu)調(diào)節(jié)劑(PAM)，Ki分別0.3and1.3nM，但在α1和α5受體亞型上效果較差。AZD7325?種中等CYP1A2和強(qiáng)效CYP3A4誘導(dǎo)劑。AZD7325具有?于焦慮和dravet綜合征相關(guān)研究的潛?。IC50&TargetCYP1A2CYP3A4體外研究AZD7325isahighaffinityandselectivemodulatoroftheGABAAreceptorsystem,exhibitshighbindingaffinityatGABAAα1,α2andα3(Ki=0.5,0.3,and1.3nM,respectively),andlowatGABAAα5(Ki=230nM)[4].AZD7325(0-10μM;3consecutivedays;oncedaily)causesamaximalCYP1A2mRNAexpressionof3.2-fold,2.1-fold,and2.5-foldinhumanhepatocytesfromdonorHH210,HH215,andHH216,respectively[2].AZD7325(0-10μM;3consecutivedays;oncedaily)causesCYP1A2andCYP3A4proteinexpressioninhumanhepatocytesfromdonorHH210[2].RT-PCR[2]CellLine:Primaryhumanhepatocytesfromonefemale(HH210)andtwomale(HH215,HH216)donorsConcentration:0.01,0.1,1,10μMIncubationTime:3consecutivedaysResult:LedtoincreaseofCYP1A2mRNAexpressionWesternBlotAnalysis[2]CellLine:PrimaryhumanhepatocytesfromdonorsConcentration:0.01,0.1,1,10μMIncubationTime:3consecutivedaysResult:IncreasedCYP1A2andCYP3A4proteinlevel.體內(nèi)研究AZD7325(oraladministration;10,17.8or31.6mg/kg;30minutesbeforetheinductionofhyperthermia)attenuateshyperthermia-inducedseizures,showsmedianthresholdsinthetreatmentgroupsof42.8°Cfor10mg/kg,43.3°Cfor17.8mg/kg,and43.4°Cfor31.6mg/kgcomparesto42.2°Cinvehiclegroup[3].AnimalModel:MaleandfemaleP18-P20F1.Scn1a+/-mice[3]2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEDosage:10,17.8or31.6mg/kgAdministration:Oraladministration;30minutesbeforetheinductionofhyperthermiaResult:Attenuatedhyperthermia-inducedseizuresinF1.Scn1a+/-micewithnosedativeeffect.REFERENCES[1].ChenX,etal.ThecentralnervoussystemeffectsofthepartialGABA-Aα2,3-selectivereceptormodulatorAZD7325incomparisonwithlorazepaminhealthymales.BrJClinPharmacol.2014Dec;78(6):1298-314.[2].ZhouD,etal.AclinicalstudytoassessCYP1A2andCYP3A4inductionbyAZD7325,aselectiveGABA(A)receptormodulator-aninvitroandinvivocomparison.BrJClinPharmacol.2012Jul;74(1):98-108.[3].NomuraT,etal.Potentiatingα2subunitcontainingperisomaticGABAAreceptorsprotectsagainstseizuresinamousemodelofDravetsyndrome.JPhysiol.2019Aug;597(16):4293-4307.[4].AZD7325,Mechanismofaction:Gamma-aminobutyricacidreceptorAalpha2&3(GABAAα2,3)positivemodulatorMcePdfHeightCaution:Product