Lesogaberan-hydrochloride-AZD-3355-hydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemELesogaberanhydrochlorideCat.No.:HY-10061BSynonyms:AZD-3355hydrochloride分?式:C?H??ClFNO?P分?量:177.54作?靶點(diǎn):GABAReceptor作?通路:MembraneTransporter/IonChannel;NeuronalSignaling儲(chǔ)存?式:4°C,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:240mg/mL(1351.81mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM5.6325mL28.1627mL56.3253mL5mM1.1265mL5.6325mL11.2651mL10mM0.5633mL2.8163mL5.6325mL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(storedundernitrogen)。-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.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥6mg/mL(33.80mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥6mg/mL(33.80mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥6mg/mL(33.80mM);ClearsolutionBIOLOGICALACTIVITY?物活性Lesogaberan(AZD-3355)hydrochloride?種有效的選擇性GABAB受體激動(dòng)劑，對(duì)?重組GABAB受體的EC50為8.6nM。通過(guò)腦膜中[3H]GABA結(jié)合位移測(cè)量，Lesogaberanhydrochloride對(duì)??GABAB和GABAA受體的親和?(Kis)：分別為5.1nM和1.4μM。Lesogaberanhydrochloride通過(guò)外周作?模式抑制短暫的?管下括約肌松弛[1]。IC50&TargetKi:5.1±1.2nM(ratGABAB),1.4±0.3μM(ratGABAA)[1]EC50:8.6±0.77nM(humanGABABreceptor)[1]體外研究Lesogaberanhydrochloride(3-30nM)enhanceshumanisletcellproliferationinvitro[2].CellProliferationAssay[2]CellLine:HumanisletcellsConcentration:3,10,and30nMIncubationTime:4daysResult:Hadasmallbutnonsignificantpromitoticeffectat3?nM,whiletreatmentathigherdosages(10and30?nM)ledtoa2-3-foldincreaseinproliferationrelativetothatofisletsculturedinmediumalone.體內(nèi)研究LesogaberanhydrochloridepotentlystimulatesrecombinanthumanGABABreceptorsandinhibitstransientloweresophagealsphincterrelaxation(TLESR)indogs,withabiphasicdose-responsecurve[1].OralLesogaberan(0.08?mg/mL;48hours)hydrochlorideprotectshumanisletβ-cellsfromapoptosisinisletgraftsinmice[2].Lesogaberan(7μmol/kg)hydrochlorideshowshighoralavailability(88%inthedogand100%intherat)andrelativelylowsystemicclearanceinfemaleSpragueDawleyrats[1].AnimalModel:DiabeticNOD/scidmicewereimplantedwithhumanislets[2]Dosage:0.08?mg/mLAdministration:48hoursResult:Significantlyreducedthepercentagesofapoptoticisletcellsandincreasedthefrequencyofinsulin+β-cellsinhumanisletgrafts.AnimalModel:FemaleSpragueDawleyrats[1]2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEDosage:7μmol/kg(PharmacokineticAnalysis)Administration:OralResult:Highoralavailability(88%inthedogand100%intherat)andrelativelylowsystemicclearance.Plasmaproteinbindingwas1%inratandhumanplasma.REFERENCES[1].LehmannA,etal.(R)-(3-amino-2-fluoropropyl)phosphinicacid(AZD3355),anovelGABABreceptoragonist,inhibitstransientloweresophagealsphincterrelaxationthroughaperipheralmodeofaction.JPharmacolExpTher.2009Nov;331(2):504-12.[2].TianJ,etal.RepurposingLesogaberantoPromoteHumanIsletCellSurvivalandβ-CellReplication.JDiabetesRes.2017;2017:6403539.McePdfHeightCaution:Producthas