SLC6A19-IN-4-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESLC6A19-IN-4Cat.No.:HY-179581CASNo.:2962069-39-0分⼦式:C₁₆H₁₆F₃N₃O₃分⼦量:355.31作⽤靶点:AminoacidTransporter作⽤通路:MembraneTransporter/IonChannel储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性SLC6A19-IN-4⼀种变构竞争性且具有⼝服活性的B0AT1(SLC6A19)抑制剂。SLC6A19-IN-4对⼈和⼩⿏的B0AT1均具有抑制活性，IC50值分别为513nM和295nM。SLC6A19-IN-4表现出优异的代谢稳定性。SLC6A19-IN-4通过对肠道(减少吸收)和肾脏(促进排泄)中B0AT1的双重抑制，能显著增加尿液中苯丙氨酸(Phe)的排泄并降低⾎浆Phe⽔平。SLC6A19-IN-4可⽤于苯丙酮尿症(PKU)及其他涉及SLC6家族转运蛋⽩疾病的研究[1]。体外研究SLC6A19-IN-4(1500-4000nM)increasestheKmford5-PhewithoutaffectingVmax,indicatingcompetitiveinhibition(Km=0.866,5.19,12.1mMVmax=337,351,380μmol/min/mg-protein)intheJump-InTIplatformcellsexpressinghumanSLC6A19andhumanCollectrin[1].SLC6A19-IN-4revealedKd=123.1nMformockcellandmB⁰AT1andACE2-expressingcellandKd=46.98nMinmockcellandhB⁰AT1andACE2-expressingcell[1].体内研究SLC6A19-IN-4(30mg/kg,p.o.,once)reducesintestinalPheabsorptionpromotesurinaryexcretionandlowerssystemicPhelevelsinmalePahenu2micecarryahomozygousF263[1].AnimalModel:MalePahenu2mice(12weeks)carryahomozygousF263[1]Dosage:30mg/kgAdministration:p.o.,onceResult:Hadaplasmaconcentrationof915ng/mland1590ng/mlat4and8hourspost-dose.Showedlowmembranepermeability24.2×10-7cm/s.1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEIncreasedurinaryPheexcretionandconcomitantlyreducedplasmaPheconcentrations4hoursafterdosing.REFERENCES[1].TakuyaImazu,etal.,Structure-guideddevelopmentofapotenthumanB0AT1inhibitoreffectiveinamousemodelofphenylketonuria.bioRxiv.2084712McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Forresearchuseonly.Tel:400-820-379