Morphothiadin-GLS4-DataSheet-生命科学试剂-MedChemExpressVIP

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMorphothiadinCat.No.:HY-108917CASNo.:1092970-12-1Synonyms:GLS4分⼦式:C₂₁H₂₂BrFN₄O₃S分⼦量:509.39作⽤靶点:HBV作⽤通路:Anti-infection储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:62.5mg/mL(122.70mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.9631mL9.8157mL19.6313mL5mM0.3926mL1.9631mL3.9263mL10mM0.1963mL0.9816mL1.9631mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥3mg/mL(5.89mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥3mg/mL(5.89mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Morphothiadin野⽣型和阿德福韦耐药HBV复制的有效抑制剂，其IC50值为12nM。IC50&TargetIC50:12nM(HBV)[1]体外研究Morphothiadinisapotentinhibitoronthereplicationofbothwild-typeandadefovir-resistantHBVwithanIC50of12nM.Morphothiadin(GLS4)showsnotoxicityupto25μM.Thecytotoxicdosewhereby50%ofcellsdie(CC50)forprimaryhepatocytesis115μMforMorphothiadin(P90is190μMforMorphothiadin(P[2].体内研究Theareaundertheconcentration-timecurvefrom0to24h(AUC0-24)ofMorphothiadin(GLS4)is556h•ng/mL.Afterintravenousadministrationof10mg/kgMorphothiadin,thetotalplasmaclearanceandapparentvolumedistributionare4.2liters/h/kgand7.38liters/kg,respectively.ThebioavailabilityofMorphothiadinis25.5%.Itisfoundthatvirustitershaveincreased83.5-foldinmicetreatedwith3.75mg/kgperdayofMorphothiadin,28.3-foldamongmicetreatedwith7.5mg/kgperday,butonly3-to6-foldamongmicetreatedwiththehigherdosesofMorphothiadin.ThereisgenerallyaninverserelationshipbetweenMorphothiadindoseandvirustiter,withthegreatestreboundseeninmicetreatedwith3.75mg/kgperdayofMorphothiadin(540-fold)andthesmallestreboundinmicetreatedwith60mg/kgperday(23-fold)(P7.5mg/kgperdaysignificantlysuppressesthevirusreplicationcyclethroughoutthetreatmentperiod,whileMorphothiadindosesof>15mg/kgperdaysuppressesvirusforupto2weeksaftertheendoftreatment[2].PROTOCOLCellAssay[2]HepAD38cellsaregrowntoabout80%confluencein0.3μg/mLoftetracycline(TET).AftertheremovalofTET,thecellsaretreatedwithdifferentdosesofMorphothiadin(GLS4),ornodrug.Cellviabilityismonitoredby3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazoliumbromide(MTT)assay[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalICRmiceareusedtoevaluatethepharmacokinetic(PK)propertiesofMorphothiadin(GLS4).FollowingoralAdministration[2]administrationof10mg/kg(ofbodyweight)ofMorphothiadintomalemice,theconcentrationofMorphothiadininplasmaisdeterminedusingliquidchromatography-tandemmassspectrometry(LC/MS/MS).Fortoxicitystudies,ICRmicearegivenMorphothiadinbygavageovera4-weekperiodandthenkeptoffdrugforanother2weeks.Groupsconsistingof20maleplus20femalemiceareadministeredavehicle(1%methyl-2-hydroxyethylcellulose),35.7,118.9,or356.6mg/kgperdayinavolumecorrespondingto20mL/kg.Tenmiceperdosegroupareeuthanized2weeksaftertheendofdrugtreatment.Bodyweight,foodconsumption,serumalbuminlevels,andadverseeffectsaredetermined[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE户使⽤本产品发表的科研⽂献•EmergMicrobesInfect.2020Dec9;1-22.•CellMolGastroenterolHepatol.2021Dec8;S2352-345X(21)00249-6.•PLoSPathog.2021Aug9;17(8):e1009838.•JVirol.2022Oct13;e0136222.•AnalMethods.2021Dec17.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ZhouX,etal.EffectsofketoconazoleandrifampicinonthepharmacokineticsofGLS4,anovelanti-hepatitisBviruscompound,indogs.ActaPharmacolSin.2013Nov;34(11):1420-6.[2].WuG,etal.PreclinicalcharacterizationofGLS4,aninhibitorofhepatitisBviruscoreparticleassembly.AntimicrobAgentsChemother.2013