JNJ-63533054-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEJNJ-63533054Cat.No.:HY-19838CASNo.:1802326-66-4分⼦式:C₁₇H₁₇ClN₂O₂分⼦量:316.78作⽤靶点:GPR139作⽤通路:GPCR/GProtein;NeuronalSignaling储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥50mg/mL(157.84mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM3.1568mL15.7838mL31.5676mL5mM0.6314mL3.1568mL6.3135mL10mM0.3157mL1.5784mL3.1568mL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%saline1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(7.89mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.89mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性JNJ-63533054⼀种有效的，选择性的，具有⼝服活性的GPR139激动剂，对⼈GPR139的EC50为16nM。JNJ-63533054对GPR139的选择性⾼于其他GPCR，离⼦通道和转运蛋⽩。JNJ-63533054可以穿过⾎脑屏障(BBB)。IC50&TargetEC50:16nM(HumanGPR139),63nM(RatGPR139)and28nM(MouseGPR139)[1]体外研究JNJ-63533054specificallyactivateshumanGPR139inthecalciummobilization(EC50of16nM)andGTPγSbinding(EC50of17nM)assays.JNJ-63533054alsoactivatestheratandmouseGPR139receptorwithsimilarpotency(ratEC50of63nM,mouseEC50of28nM)[1].InasaturationstudyforhumanGPR139,asinglepopulationofhigh-affinitybindingsitesfor[3H]JNJ-63533054isobserved(Kdof10nM).TheBmaxvalueis26pmol/mgofprotein.SaturationstudiesfortheratGPR139andmouseGPR139yieldedKdvalueswithinthesamerange(32nMand23nM,respectively;Bmax=8.5pmol/mgofproteinand6.2pmol/mgofprotein,respectively)[1].体内研究JNJ-63533054(3-30mg/kg;oraladministration;once;SDrats)treatmentinducesadose-dependentreductioninlocomotoractivityinthefirsthour[1].ThepharmacokineticsofJNJ-63533054(Compound7c;1mg/kgiv;5mg/kgpo)inratisexamined.TheIVclearanceis53mL/min/kg,theCmaxis317ng/mL(~1μM),thet1/2is2.5hours,andJNJ-63533054isabletocrosstheblood-brainbarrier(BBB)withabraintoplasmaratio(b/p)of1.2[2].AnimalModel:MaleSprague-Dawleyrats(350-450g)[1]Dosage:3mg/kg,10mg/kg,and30mg/kgAdministration:Oraladministration;onceResult:Inducedadose-dependentreductioninlocomotoractivityinthefirsthour.REFERENCES[1].DvorakCA,etal.IdentificationandSARofGlycineBenzamidesasPotentAgonistsfortheGPR139Receptor.ACSMedChemLett.2015Jul20;6(9):1015-8.[2].LiuC,etal.GPR139,anOrphanReceptorHighlyEnrichedintheHabenulaandSeptum,IsActivatedbytheEssentialAminoAcidsL-TryptophanandL-Phenylalanine.MolPharmacol.2015Nov;88(5):911-25.McePdfHeightCaution:Producthasnotbeenfullyvalidatedf