Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGS-441524Cat.No.:HY-103586CASNo.:1191237-69-0分?式:C??H??N?O?分?量:291.26作?靶點:DNA/RNASynthesis;SARS-CoV作?通路:CellCycle/DNADamage;Anti-infection儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:83.33mg/mL(286.10mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.4334mL17.1668mL34.3336mL5mM0.6867mL3.4334mL6.8667mL10mM0.3433mL1.7167mL3.4334mL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(fù)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%salineSolubility:≥2.08mg/mL(7.14mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(7.14mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(7.14mM);Clearsolution4.請依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.75mg/mL(9.44mM);Clearsolution5.請依序添加每種溶劑：5%ethanol,30%propyleneglycol,45%PEG400,20%water(pH1.5withHCI)Solubility:10mg/mL(34.33mM);Clearsolution;NeedultrasonicandadjustpHto2withHClBIOLOGICALACTIVITY?物活性GS-441524Remdesivir的主活性代謝物，活性更優(yōu)于Remdesivir，感染冠狀病毒的原代?肺和貓細胞的細胞模型中顯?出相似的活性。GS-441524對貓傳染性腹膜炎病毒(FIPV)有較強的抑制作?，對應(yīng)的EC50值為0.78μM。IC50&TargetEC50:0.78μM(FIPV)[1].體外研究ThecellsappearandgrownormallyatallconcentrationsofGS-441524andfailtouptakethefluorescentdyeCellToxGreenat24h.Thecytotoxicconcentration-50%(CC50)istherefore>100μM.Theeffectiveconcentration-50%(EC50)ofGS-441524iscalculatedtobe0.78μM[1].體內(nèi)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?邊的抑制劑?師www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?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.