Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemETRPV1antagonist10Cat.No.:HY-172774CASNo.:896584-55-7分子式:C??H??N?O?分子量:314.29作用靶點(diǎn):TRPChannel;URAT1;GLUT;CytochromeP450作用通路:MembraneTransporter/IonChannel;NeuronalSignaling;MetabolicEnzyme/Protease儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性TRPV1antagonist10是一種口服有效的強(qiáng)效TRPV1拮抗劑(IC50=33.06nM)，以及中度至弱效的URAT1(IC50=22.51μM)和GLUT9(50μM時(shí)為60.25%)抑制劑。TRPV1antagonist10具有鎮(zhèn)痛、降尿酸作用。TRPV1antagonist10可用于研究高尿酸血癥和炎癥性疼痛[1]。IC50&TargetTRPV1TRPV3TRPV4TRPA136.47nM(IC50)>100μM(IC50)>100μM(IC50)>100μM(IC50)TRPM8CYP1A2CYP2C9CYP2C196.47μM(IC50)28.31μM(IC50)42.85μM(IC50)9.23μM(IC50)CYP2D6CYP3A4M>100μM(IC50)8.73μM(IC50)體外研究TRPV1antagonist10(Compound39)(50μM,24h)shows60.25%inhibitionrateagainstGLUT9inUA(1mM)-treatedHEK293Tcells[1].TRPV1antagonist10(0-400μM,24-72h)exhibitshigherlevelsofcytotoxicityonHepG2andHK2cellswithincreasingdoseandtimeofincubation[1].TRPV1antagonist10(0-100μM,3-20min)showshighmetabolicstabilityinhumanandratlivermicrosomes[1].CellCytotoxicityAssay[1]CellLine:HepG2andHK2celllines1/2 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEConcentration:0-400μMIncubationTime:24or72hincubationResult:ExhibitedlittlecytotoxicityinHepG2cellsafter24hincubation.Causedsignificantcytotoxicityattheconcentrationof50μMafter72hincubationinHepG2cells.LedtosignificantinhibitionofcellviabilityinHK2celllineat200μMand24hincubation.HadslightlylesstoxicityinbothcelllinesincomparisontoBenzbromaron(HY-B1135).體內(nèi)研究TRPV1antagonist10(Compound39)(3-20mg/kg,p.o.,onesingledose)showsdose-dependentanalgesiceffectinbothFormalin-inducedphaseIandphaseIIpaininmaleKunmingmicemodel[1].TRPV1antagonist10(10-20mg/kg,p.o.,21consecutivedays)reducestheuricacidlevelandimprovestherenalfunctionat20mg/kginhyperuricemiamicemodel[1].TRPV1antagonist10(500mg/kg,p.o.,onesingledose)leadstonoobviousabnormalbehaviorsanddifferenceinweightandfoodintakeinhealthyKunmingmice[1].TRPV1antagonist10(100mg/kg,p.o.,everyotherdayfor14consecutivedays)leadstonoobviousabnormalbehaviorsanddifferenceinweightandfoodintakeinhealthyKunmingmice[1].AnimalModel:MaleKunmingmice,5%Formalin(injectedsubcutaneouslyintotherightreartoe)-inducedpersistentpainmodel(8weeks,22-25g)[1]Dosage:3mg/kg,10mg/kg,20mg/kgAdministration:Oralgavage(p.o.),onesingledoseResult:Showednoobviousanti-nociceptiveactivityatdoseof3mg/kgand10mg/kg.Exhibitedsignificantlybetteranalgesiceffectwith20mg/kgdosageinphaseI(0-5min)andphaseII(6-45min)pain.AnimalModel:MaleKunminghyperuricemiamicemodel(8weeks,22-25g)[1]Dosage:10mg/kg,20mg/kgAdministration:Oralgavage(p.o.),21consecutivedaysResult:Reducedinflammatorycytokines(IL-1β,TNF-α,andIL-6)withbothdosages.Reducedthelevelofrenalinterstitialfibrosisafter21continuousdays.REFERENCESChunxiaLiu,etal.,StructureOptimizationofNaturalProductPiperinetoObtainNovelandPotentAnalogswithAnti-inflammationPainandUrate-LoweringEffect,EuropeanJournalofMedicinalChemistry,2025,117649,ISSN0223-5234McePdfHeight2/2 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemECaution:Producthasnot