NCS-382-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemENCS-382Cat.No.:HY-101207CASNo.:520505-01-5分子式:C₁₃H₁₄O₃分子量:218.25作用靶点:GABAReceptor作用通路:MembraneTransporter/IonChannel;NeuronalSignaling储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性NCS-382是一种有效的GABA受体拮抗剂，也是GHBR受体拮抗剂。NCS-382具有抗惊厥，抗镇静活性。NCS-382可用于遗传性神经系统疾病的相关研究[1][4]。体外研究NCS-382(0.5nM,24h)showsnocapacityforinhibitionofmicrosomalCYPs(CYP1A2,2B6,2C8,2C9,2C19,2D6and3A4)andminimalpotentialforactivationofxenobioticnuclearreceptorsinHepG2cells[2].NCS-382(0.01-1000μM,24h)showslowprobabilityofcellulartoxicityinHepG2cells[2].NCS-382isaGHBRantagonistwithIC50sof134.1nMand201.3nMinisolatedratstriatumandhippocampusmembranes,respectively[4].CellCytotoxicityAssay[2]CellLine:HepG2cellsConcentration:0.01-1000μMIncubationTime:24hResult:ReducedHepG2cellviabilityataconcentrationof1mM,andthissameconcentrationdidnotinduceapoptosisorcytotoxicityinHepG2cells.体内研究NCS-382(100,300,500mg/kg;i.p.)showsatadoseof100mg/kghasamaximumserumconcentrationthatis4timesthatofthebrainand10timesthatofthekidney,andamaximumliverconcentrationthatismorethan700%higherthantheseruminmousemodel[1].Atadoseof500mg/kg,itmaypreferentiallyresideintheliverafterintraperitonealadministrationinmouse1/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEmodel[1].Atadoseof500mg/kg,brainpermeabilityimproves,asevidencedbyanincreaseinbrainserumratioinmousemodel[1].NCS-382(0.83-2.08mmol/kg;i.p.)reducesGHB-inducedincreasesinthetimemicespentimmobileintheforcedswimtest,indicatinganti-sedativeactivity,whenadministeredatdosesof1.66and2.08mmol/kginmicemodel[3].NCS-382(2.3mmol/kg;i.p.)decreasesspikeandwavedischargesinaudiogenicseizure-susceptibleSwissRbmice,aswellasaratmodelofpetitmalepilepsy[4].Pharmacokineticanalysisofmouseserumandtissueatadoseof100mg/kg[1]在剂量100mg/kg下小鼠血清和组织的药代动力学分析[1]TissueDose(mg/kg)AUC(μg•h/L)Cmax(μmol/L)T1/2(h)Serum1001192410.243Brain100139600.967Liver10011501695/Kidney10024.523.60.308Pharmacokineticanalysisofmouseserumandtissueatadoseof300mg/kg[1]在剂量300mg/kg下小鼠血清和组织的药代动力学分析[1]TissueDose(mg/kg)AUC(μg•h/L)Cmax(μmol/L)T1/2(h)Serum3004363740.468Brain3003131410.883Liver300///Kidney300///Pharmacokineticanalysisofmouseserumandtissueatadoseof500mg/kg[1]在剂量500mg/kg下小鼠血清和组织的药代动力学分析[1]TissueDose(mg/kg)AUC(μg•h/L)Cmax(μmol/L)T1/2(h)Serum5007174510.683Brain50012805300.761Liver500///Kidney500///AnimalModel:GBLinducedmousemodel[1]Dosage:300mg/kg(Combinedwithdiclofenac(25mg/kg))Administration:Intraperitonealinjection(i.p.),Thirtyminuteslater,miceweregivenani.p.injectionofGBL(100mg/kgdilutedinPBS)Result:Inthepresenceofdiclofenac,itwashighlyprotectiveagainstGBLmediatedresponses.AnimalModel:GBLinducedmousemodel[3]Dosage:0.83,1.25,1.66,2.08mmol/kgAdministration:Intraperitonealinjection(i.p.),30minbeforethetestResult:Atadosageof2.08mmol/kg,completelyblockedtheeffectofGHBwhenadministeredat3.18mmol/kgREFERENCES[1].AinslieGR,etal.ApharmacokineticevaluationandmetaboliteidentificationoftheGHBreceptorantagonistNCS-382inmouseinforms2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEnoveltherapeuticstrategiesforthetreatmentofGHBintoxication.PharmacolResPerspect.2016Oct18;4(6):e00265.VogelKR,etal.InvitrotoxicologicalevaluationofNCS-382,ahigh-affinityantagonistofγ-hydroxybutyrate(GHB)binding.ToxicolInVitro.2017Apr;40:196-202SchmidtC,etal.Anti-sedativeandanti-catalepticpropertiesofNCS-382,agamma-hydroxybutyratereceptorantagonist.EurJPharmacol.1991Oct22;203(3):393-7.MaitreM,HechlerV,VayerP,GobailleS,CashCD,SchmittM,BourguignonJJ.Aspecificgamma-hydroxybutyratereceptorligandpossessesbothantagonisticandanticonvulsantproperties.JPharmacolExpTher.1990Nov;255(2):657-63.M