Acoramidis-hydrochloride-AG10-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAcoramidishydrochlorideCat.No.:HY-109165ACASNo.:2242751-53-5Synonyms:AG10hydrochloride分⼦式:C₁₅H₁₈ClFN₂O₃分⼦量:328.77作⽤靶点:Others作⽤通路:Others储存⽅式:Powder-20°C3yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:62.5mg/mL(190.10mM;Needultrasonic)H2O:<0.1mg/mL(ultrasonic;warming;heatto60°C)(insoluble)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.0416mL15.2082mL30.4164mL5mM0.6083mL3.0416mL6.0833mL10mM0.3042mL1.5208mL3.0416mL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%saline1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.08mg/mL(6.33mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(6.33mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(6.33mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Acoramidis(AG10)hydrochloride具有⼝服活性的、选择性的甲状腺素转运蛋⽩(TTR(transthyretin))的稳定剂，对野⽣型和V1221突变型均有效。Acoramidis(AG10)hydrochloride可⽤于转体甲状腺素淀粉样变性的研究。体外研究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