AZD7325-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAZD7325Cat.No.:HY-111052CASNo.:942437-37-8分⼦式:C₁₉H₁₉FN₄O₂分⼦量:354.38作⽤靶点:GABAReceptor;CytochromeP450作⽤通路:MembraneTransporter/IonChannel;NeuronalSignaling;MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:250mg/mL(705.46mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.8218mL14.1091mL28.2183mL5mM0.5644mL2.8218mL5.6437mL10mM0.2822mL1.4109mL2.8218mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.08mg/mL(5.87mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(5.87mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性AZD7325具有⼝服活性的α2,3receptor的正向别构调节剂(PAM)，Ki分别0.3and1.3nM，但在α1和α5受体亚型上效果较差。AZD7325⼀种中等CYP1A2和强效CYP3A4诱导剂。AZD7325具有⽤于焦虑和dravet综合征相关研究的潜⼒。IC50&TargetCYP1A2CYP3A4体外研究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.体内研究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—您⾝边的抑制剂⼤师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