P2Y14R-antagonist-1-生命科學試劑-MCE

Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEP2Y14Rantagonist1Cat.No.:HY-161727CASNo.:2728291-29-8分子式:C??H??BrN?O?分子量:346.18作用靶點:P2YReceptor;NOD-likeReceptor(NLR)作用通路:GPCR/GProtein;Immunology/Inflammation儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性 P2Y14Rantagonist1(compoundI-17)是一種強效選擇性P2Y14R拮抗劑，其IC50為0.6nM。P2Y14Rantagonist1表現(xiàn)出強效的P2Y14R拮抗活性，以及體內(nèi)外的有效性和良好的藥代動力學特性。P2Y14Rantagonist1通過NOD樣受體家族瘤病毒蛋白(NLRP3)/瘤病毒蛋白D(GSDMD)信號通路減少炎癥因子的釋放和細胞焦亡。P2Y14Rantagonist1有望用于急性痛風性關(guān)節(jié)炎領(lǐng)域的研究[1]。IC50&TargetP2Y14ReceptorP2Y2ReceptorP2Y6ReceptorP2Y12Receptor0.6nM(IC50)>100nM(IC50)89.7nM(IC50)>100nM(IC50)P2Y1ReceptorNLRP3>100nM(IC50)體外研究P2Y14Rantagonist1(compoundI-17)(2-256μM,24h)showsnosignificantcytotoxicityinRAW264.7cellsatconcentrationsbelow256μM[1].P2Y14Rantagonist1(10-40μM,1h)cancounteracttheeffectsofMSUandLPS,demonstratinganti-goutinflammatoryproperties[1].P2Y14Rantagonist1(10-40μM,1h)actsupstreamoftheNLRP3inflammasomeassembly,inhibitingsubsequentcaspase-1activationandmacrophagepyroptosis[1].CellViabilityAssay[1]CellLine:RAW264.7cellsConcentration:2-256μM1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEIncubationTime:24hResult:Onlyexhibitedsignificantcytotoxicityonlyatadoseof256μM.WesternBlotAnalysis[1]CellLine:RAW264.7cellsConcentration:10-40μMIncubationTime:1hResult:InhibitedtheexpressionofNLRP3andGSDMDinMSU-andLPS-treatedRAW264.7cells.Immunofluorescence[1]CellLine:RAW264.7cellsConcentration:10-40μMIncubationTime:1hResult:SignificantlyreducedtheformationofASCspecksinducedbyMSUandLPS.體內(nèi)研究P2Y14Rantagonist1(compoundI-17)(5-20mg/mL,i.p.,1h)canpromotetheinflammatoryresponsecausedbyMSUcrystalinjection-inducedacutegoutyarthritisintheMSU-inducedmousegoutmodel[1].1.19PharmacokineticAnalysisinMC38SyngeneicModel[1]藥代動力學分析[1]P2Y14Rantagonist1Cmax(g/mL)T1/2(h)Tmax(h)AUC0-∞(h?ng/mL)CL(L/h/kg)F(%)i.v.(10mg/kg)15337.61817653.5p.o.(30mg/kg)289512.6032284514.8075AnimalModel:Acutegoutyarthritismodel[1]Dosage:5-20mg/mLAdministration:Intraperitonealinjection(i.p.),60minResult:EffectivelyreducedpawswellingintheMSU-inducedmousegoutmodel,significantlydecreasedtheproductionofpro-inflammatorycytokinesIL-1β,IL-6,andIL-18inducedbyMSU,markedlyinhibitedinflammatorycellinfiltrationinfoottissuesinducedbyMSU,andsignificantlysuppressedtheincreaseofNLRP3inducedbyMSU.REFERENCES2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemELiuW,etal.DiscoveryofN-SubstitutedAcetamideDerivativesasPromisingP2Y14RAntagonistsUsingMolecularHybridizationBasedonCrystallographicOverlay.JMedChem.2024Jun27;67(12):10233-10247.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformed