Acoramidis-hydrochloride-AG10-hydrochloride-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAcoramidishydrochlorideCat.No.:HY-109165ACASNo.:2242751-53-5Synonyms:AG10hydrochloride分?式:C??H??ClFN?O?分?量:328.77作?靶點:Others作?通路:Others儲存?式:Powder-20°C3yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:62.5mg/mL(190.10mM;Needultrasonic)H2O:<0.1mg/mL(ultrasonic;warming;heatto60°C)(insoluble)MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.0416mL15.2082mL30.4164mL5mM0.6083mL3.0416mL6.0833mL10mM0.3042mL1.5208mL3.0416mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(6.33mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(6.33mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(6.33mM);ClearsolutionBIOLOGICALACTIVITY?物活性Acoramidis(AG10)hydrochloride具有?服活性的、選擇性的甲狀腺素轉(zhuǎn)運蛋?(TTR(transthyretin))的穩(wěn)定劑，對野?型和V1221突變型均有效。Acoramidis(AG10)hydrochloride可?于轉(zhuǎn)體甲狀腺素淀粉樣變性的研究。體外研究Acoramidis(AG10,0.1-10μMforTTR-5μM)stabilizesV122I-andWT-TTRequallywellandalsoexceedstheirefficacytostabilizeWTandmutantTTRinwholeserum[1].Acoramidis(AG10)stimulatesthemitochondrialQO2inaconcentration-dependentmannerbetween10and100μM[3].Acoramidis(AG10)hasveryminimalinhibitionoftwocommonoff-targetsindrugdiscovery,thepotassiumionchannelhERG(IC50>100μM)andanumberofcytochromeP450isozymes(IC50>50μM)(lowtoxicity)[1].WesternBlotAnalysis[1].CellLine:Humanserum(TTR-5μM).Concentration:0.1and10μM.IncubationTime:72h.Result:WassignificantlymoreeffectivethantafamidisinstabilizingTTR.TheconcentrationofAG10to10μMresultedinstabilizationofalmostallofTTRinserum.REFERENCES[1].SravanCPenchala,etal.AG10inhibitsamyloidogenesisandcellulartoxicityofthefamilialamyloidcardiomyopathy-associatedV122Itransthyretin.ProcNatlAcadSciUSA.2013Jun11;110(24):9992-7.[2].JonathanCFox,etal.First-in-HumanStudyofAG10,aNovel,Oral,Specific,Selective,andPotentTransthyretinStabilizerfortheTreatmentofTransthyretinAmyloidosis:APhase1Safety,Tolerability,Pharmacokinetic,andPharmacodynamicStudyinHealthyAdultVolunteers.ClinPharmacolDrugDev.2020Jan;9(1):115-129.[3].StephenPSoltoff,etal.EvidencethattyrphostinsAG10andAG18aremitochondrialuncouplersthatalterphosphorylation-dependentcellsignaling.JBiolChem.2004Mar19;279(12):10910-8.McePdfHeightCaution:Producthasnotbeenfullyvalidatedforme