BI-689648-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBI689648Cat.No.:HY-101217CASNo.:1633009-87-6分⼦式:C₁₆H₁₈N₄O₂分⼦量:298.34作⽤靶点:CytochromeP450作⽤通路:MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:30mg/mL(100.56mM;Needultrasonicandwarming)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.3519mL16.7594mL33.5188mL5mM0.6704mL3.3519mL6.7038mL10mM0.3352mL1.6759mL3.3519mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(8.38mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(8.38mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(8.38mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性BI689648⼀种新型的，⾼选择性醛酮合酶抑制剂，能抑制CYP11B1和CYP11B2，其IC50值分别为310和2.1nM。IC50&TargetIC50:310nM(CYP11B1),2.1nM(CYP11B2)[1]体外研究ComparewiththeFADsandLCI699,BI689648ishighlyselectiveinvitro,providinganIC50forCYP11B2of2.1nMandaselectivityfactorof149overCYP11B1.FAD286,bycomparison,showsasimilarIC50forCYP11B2(2.5nM);however,itsgreaterpotencyagainstCYP11B1(94nM)resultsinacomparativelymodestselectivityfactorof38,approximately4-foldlessthanBI689648[1].体内研究Afteroraladministrationincynomonkeys,BI689648(5mg/kg)exhibitsapeakplasmaconcentrationof~500nM.ForBI689648(aldosteroneEC50=2nM),appreciablechangesin11-DOCareonlynotedatplasmaconcentrations>2000nMor>1000-folditsaldosteroneEC50whileFAD286showsawindowof~100-fold.BI689648exhibitsminimalimpacton11-DCandonlyatveryhighplasmaconcentrations(~10μM)[1].PROTOCOLCellAssay[1]Homogenizedadrenalglandsareusedtoevaluatetestcompounds(includingBI689648)ina96-wellplateformat.Amixtureofconcentratedhomogenateandsubstrateisaddedtocompounddilutionsforanalysis.ValuesfortheconcentrationrequiredtoinhibitCS(CYP11B1)andAS(CYP11B2)enzymeactivityby50%(IC50)arecalculated[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalForaldosteronesynthaseinhibitors(ASI)evaluation,thestudycohortconsistsof66healthyanimals.EachAdministration[1]separatestudyday,12cynomonkeysarerandomizedtoreceivevariousdosesofASIorvehiclecontrol(n=3/group);theanimalsarereusedacrossstudies,allowingaminimumof2weekswashoutbetweenstudies.Aggregationofdataacrossmultiplestudiesisusedtoderiveinvivoeffectiveconcentration(EC)valuesforaldosteroneandcortisolbycurve-fitting.Conscious,nonchairedmonkeysreceivevehicle(n=35),S-FAD(n=9),FAD286(n=24),LCI699(n=36),orBI689648(n=26)atdosesrangingfrom0.003mg/kgto10mg/kg.Maximaladrenocorticotropin(ACTH)-inducedaldosteroneandcortisolproductionoccursquickly,within15minutesafterchallenge,atwhichtimebloodiscollectedforplasmaaldosterone,cortisol,andtestcompoundconcentrations[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].WeldonSM,etal.SelectivityofBI689648,aNovel,HighlySelectiveAldosteroneSynthaseInhibitor:ComparisonwithFAD286andLCI699inNonhumanPrimates.JPharmacolExpTher.2016Oct;359(1):142-50.McePdfHeightCautio