ICA-105665-PF-04895162-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEICA-105665Cat.No.:HY-125469Synonyms:PF-04895162分⼦式:C₁₉H₁₅F₂N₃O₂分⼦量:355.34作⽤靶点:PotassiumChannel作⽤通路:MembraneTransporter/IonChannel储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性ICA-105665(PF-04895162)⼀种有效的⼝服活性的神经元Kv7.2/7.3和Kv7.3/7.5钾通道激动剂。ICA-105665抑制肝线粒体功能和胆盐输出蛋⽩(BSEP)转运(IC50为311μM).ICA-105665可穿透⾎脑屏障并具有抗癫痫作⽤。IC50&TargetKv7.2/7.3andKv7.3/7.5potassiumchannels[1][2]体外研究ICA-105665(PF-04895162)doesnotdisplaypotentcytotoxicpropertiesinTHLEandHepG2celllines(IC50~192μMand130μMafter72hours,respectively)orinhumanhepatocytes(AC50forcelllossat48hourswas>125μMbasedonresultsinthreeassessmentsintwodifferenthumanhepatocytelots(LBNandHU4165)[1].MitochondrialrespiratoryreserveiscompromisedinhumanhepatocytestreatedwithICA-105665(PF-04895162)atconcentrations>11μMfor25minutes[1].体内研究ForICA-105665(PF-04895162),ina7-dayrattoxicitystudy,dose-dependentalanineaminotransferase(ALT)elevations,potentiallyindicativeoflivertoxicity,wereobserved.However,nohistologicalevidenceofliverinjurywasidentified,andALTelevationswerenotconfirmedinarepeat7-daystudy.Further,28dayand6monthtoxicitystudiesinratswerenegativefortransaminaseelevationsandlivertoxicity,andtoxicitystudiesupto9monthsdurationincynomolgusmonkeyswerealsonegative[2].ICA-105665(PF-04895162)hasdemonstratedbroadspectrumantiseizureactivityinmultipleanimalmodelsincludingmaximalelectroshock,6Hzseizures,pentylenetetrazole,andelectricalkindlingatdosesfrom[3].REFERENCES1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].AleoMD,etal.PhaseIstudyofPF‐04895162,aKv7channelopener,revealsunexpectedhepatotoxicityinhealthysubjects,butnotratsormonkeys:clinicalevidenceofdisruptedbileacidhomeostasis.PharmacolResPerspect.2019Feb;7(1):e00467.[2].GenerauxG,etal.Quantitativesystemstoxicology(QST)reproducesspeciesdifferencesinPF-04895162liversafetyduetocombinedmitochondrialandbileacidtoxicity.PharmacolResPerspect.2019Oct9;7(6):e00523.[3].Kasteleijn-NolstTrenitéDG,etal.Kv7potassiumchannelactivationwithICA-105665reducesphotoparoxysmalEEGresponsesinpatientswithepilepsy.Epilepsia.2013Aug;54(8):1437-43.[4].BialerM,etal.Progressreportonnewantiepilepticdrugs:asummaryoftheEleventhEilatConference(EILATXI).EpilepsyRes.2013Jan;103(1):2-30.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplicati