Osilodrostat-LCI699-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEOsilodrostatCat.No.:HY-16276CASNo.:928134-65-0Synonyms:LCI699分?式:C??H??FN?分?量:227.24作?靶點(diǎn):MineralocorticoidReceptor作?通路:MetabolicEnzyme/Protease儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:250mg/mL(1100.16mM;Needultrasonic)Ethanol:100mg/mL(440.06mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM4.4006mL22.0032mL44.0063mL5mM0.8801mL4.4006mL8.8013mL10mM0.4401mL2.2003mL4.4006mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(11.00mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(11.00mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(11.00mM);Clearsolution4.請(qǐng)依序添加每種溶劑：10%EtOH>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(11.00mM);Clearsolution5.請(qǐng)依序添加每種溶劑：10%EtOH>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(11.00mM);Clearsolution6.請(qǐng)依序添加每種溶劑：10%EtOH>>90%cornoilSolubility:≥2.5mg/mL(11.00mM);ClearsolutionBIOLOGICALACTIVITY?物活性O(shè)silodrostat(LCI699)?種?服有效的11β-羥化酶(CYP11B1)抑制劑，其IC50值為35nM。Osilodrostat?種?服有效的醛酮合成酶(CYP11B2)抑制劑，抑制?醛酮合成酶和??醛酮合成酶的IC50分別為0.7nM和160nM。Osilodrostat抑制醛酮和?質(zhì)酮的合成。Osilodrostat具有降低?壓的能?。Osilodrostat可?于庫(kù)欣綜合征(CS)的研究。IC50&TargetIC50:35nM(CYP11B1),0.7nM(humanaldosteronesynthase),and160nM(rataldosteronesynthase)[1][2]體外研究Osilodrostat(LCI699;0.01-10μM;HAC15cells,17primaryhumanadrenocorticalcellcultures,andpituitaryadenomacells)inhibitscortisolandaldosterone.Osilodrostatresultsininhibitionofcorticosterone,11-deoxycortisolaccumulation,andmodesteffectsonadrenalandrogens[2].體內(nèi)研究Osilodrostat(LCI699;0.1-100mg/kg;p.o.;once)inhibitsaldosteroneandcorticosteronesynthesisinAng-II-andACTH-stimulatedSpragueDawleyrats[1].Osilodrostat(LCI699;3-100mg/kg;p.o.;daily,for52weeks)reducesmeanarterialpressureandprolongssurvivalindTGrats[1].AnimalModel:MaleAng-II-andACTH-stimulatedSpragueDawleyrats[1]Dosage:0.1,0.3,1and3mg/kg(Ang-II-stimulatedrats)and1,3,10,30and100mg/kg(ACTH-stimulatedrats)Administration:Oraladministration;onceResult:InhibitedtheincreaseinplasmaaldosteroneconcentrationsstimulatedbyAngIIorACTHinadose-dependentmanner.AnimalModel:dTGrats[1]2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEDosage:3,10,30and100mg/kgAdministration:Oraladministration;daily,for52weeksResult:IncreasedfractionalLV(systolicanddiastolic)shortening,normalizedLVisovolumicrelaxationtimetoRR(IVRT/RR)ratioandmyocardialcellsizeandreducedLVweightinadose-dependentmanner.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?ActaPharmSinB.21September2021.?BMCMed.2021Sep8;19(1):204.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MénardJ,et,al.Aldosteronesynthaseinhibition:cardiorenalprotectioninanimaldiseasemodelsandtranslationofhormonaleffectstohumansubjects.JTranslMed.2014Dec10;12:340.[2].CreemersSG,et,al.OsilodrostatIsaPotentialNovelSteroidogenesisInhibitorfortheTreatmentofCushingSyndrome:AnInVitroStudy.JClinEndocrinolMetab.2019Aug1;104(8):3437-3449.[3].LiL,et,al.Osilodrostat(LCI699),apotent11β-hydroxylaseinhibitor,administeredincombinationwiththemultireceptor-targetedsomatostatinanalogpasireotide:A13-weekstudyinrats.ToxicolApplPharmacol.2015Aug1;286(3):224-33.McePdfHeig