GS-441524-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGS-441524Cat.No.:HY-103586CASNo.:1191237-69-0分⼦式:C₁₂H₁₃N₅O₄分⼦量:291.26作⽤靶点:DNA/RNASynthesis;SARS-CoV作⽤通路:CellCycle/DNADamage;Anti-infection储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:83.33mg/mL(286.10mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.4334mL17.1668mL34.3336mL5mM0.6867mL3.4334mL6.8667mL10mM0.3433mL1.7167mL3.4334mL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:≥2.08mg/mL(7.14mM);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:≥2.08mg/mL(7.14mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(7.14mM);Clearsolution4.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.75mg/mL(9.44mM);Clearsolution5.请依序添加每种溶剂：5%ethanol,30%propyleneglycol,45%PEG400,20%water(pH1.5withHCI)Solubility:10mg/mL(34.33mM);Clearsolution;NeedultrasonicandadjustpHto2withHClBIOLOGICALACTIVITY⽣物活性GS-441524Remdesivir的主活性代谢物，活性更优于Remdesivir，感染冠状病毒的原代⼈肺和猫细胞的细胞模型中显⽰出相似的活性。GS-441524对猫传染性腹膜炎病毒(FIPV)有较强的抑制作⽤，对应的EC50值为0.78μM。IC50&TargetEC50:0.78μM(FIPV)[1].体外研究ThecellsappearandgrownormallyatallconcentrationsofGS-441524andfailtouptakethefluorescentdyeCellToxGreenat24h.Thecytotoxicconcentration-50%(CC50)istherefore>100μM.Theeffectiveconcentration-50%(EC50)ofGS-441524iscalculatedtobe0.78μM[1].体内研究All10treatedcatshavearapidresponsetotreatmentandlymphocytelevelsandrectaltemperaturesreturntopre-infectionlevelsandlevelsofthetwoasymptomaticcats.Alltenoftheonceortwicetreatedcatshaveremainednormaltodate(morethaneightmonthspostinfection).Injectionscauseatransient"stinging"reactioninsomecatswithin10sofcompoundadministration.Localizedandtransientpainisevidencedbyunusualposturing,lickingattheinjectionsiteand/orvocalizationsthatlastforapproximately30-60safterinjection.Injectionreactionsaremorepronouncedinsomeanimalsrelativetoothersandreactionsareinconsistentfromoneinjectiontothenextanddecreasovertime[1].Remdesivi(IVinjection)inNHPresultsinGS-441524beingpresentinserumatconcentrations1000-foldhigherthanRemdesivirthroughouta7-daytreatmentcourse[3].PROTOCOLCellAssayTodeterminethetoxicityofGS-441524toCRFKcellsn,CRFKcellsaretreatedwith100,33.3,11.1,3.7or1.2μMGS-441524for24h[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalCats[1]Administration[1]The10catsthatdevelopeddiseasesignsaredividedintotwogroupsandtreatedwitheither5mg/kg(GroupA;n=5)or2mg/kg(GroupB;n=5)GS-441524SCq24hstartingthreedaysafterunequivocalclinicalevidenceofFIP(days12-19postinfection).Thetwocatsthatdonotdevelopdiseasesignsserveascontrolsfornormalbloodlymphocytecountsandrectaltemperature[1].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•JMedVirol.2021Mar5.•NucleicAcidsRes.2021Jan8;49(D1):D1113-D1121.•NatCommun.2021Nov5;12(1):6415.•BiomedPharmacother.2022Nov22;157:114037.•ClinTranslSci.2021Nov10.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MurphyBG,etal.ThenucleosideanalogGS-441524stronglyinhibitsfelineinfectiousperitonitis(FIP)virusintissuecultureandexperimentalcatinfectionstudies.VetMicrobiol.2018Jun;219:226-233.[2].KatherineYang,etal.WhatDoWeKnowAboutRemdesivirDrugInteractions?ClinTranslSci.2020May13;10.1111/cts.12815.[3].VictoriaC.Yan,etal.AdvantagesoftheParentNucleosideGS-441524overRemdesivirforCovid-19Treatment.ACSMed.Chem.