Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEJNJ-63533054Cat.No.:HY-19838CASNo.:1802326-66-4分?式:C??H??ClN?O?分?量:316.78作?靶點(diǎn):GPR139作?通路:GPCR/GProtein;NeuronalSignaling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:≥50mg/mL(157.84mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.1568mL15.7838mL31.5676mL5mM0.6314mL3.1568mL6.3135mL10mM0.3157mL1.5784mL3.1568mL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(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個(gè)?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%saline1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(7.89mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.89mM);ClearsolutionBIOLOGICALACTIVITY?物活性JNJ-63533054?種有效的，選擇性的，具有?服活性的GPR139激動劑，對?GPR139的EC50為16nM。JNJ-63533054對GPR139的選擇性?于其他GPCR，離?通道和轉(zhuǎn)運(yùn)蛋?。JNJ-63533054可以穿過?腦屏障(BBB)。IC50&TargetEC50:16nM(HumanGPR139),63nM(RatGPR139)and28nM(MouseGPR139)[1]體外研究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].體內(nèi)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