Vesatolimod-GS-9620-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEVesatolimodCat.No.:HY-15601CASNo.:1228585-88-3Synonyms:GS-9620分?式:C??H??N?O?分?量:410.51作?靶點(diǎn):Toll-likeReceptor(TLR);Apoptosis;HBV;HCV;HIV作?通路:Immunology/Inflammation;Apoptosis;Anti-infection儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥16.67mg/mL(40.61mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.4360mL12.1800mL24.3599mL5mM0.4872mL2.4360mL4.8720mL10mM0.2436mL1.2180mL2.4360mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1.67mg/mL(4.07mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:1.67mg/mL(4.07mM);Suspendedsolution;Needultrasonic3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.67mg/mL(4.07mM);ClearsolutionBIOLOGICALACTIVITY?物活性Vesatolimod(GS-9620)?種有效，選擇性，可?服的Toll樣受體7(TLR7)激動(dòng)劑，EC50值為291nM。IC50&TargetEC50:291nM(TLR7),9μM(TLR8)[3]體外研究Vesatolimod(GS-9620)rapidlyinternalizesintocellsandpreferentiallylocalizestoandsignalsfromendo-lysosomalcompartments.Totestthishypothesis,thekineticsofcellularuptakeofthecompoundinDaudicellsusingtritiatedVesatolimod(3H-GS-9620)ismeasured.Thekineticsof3H-GS-9620accumulationisrapid,reachingconcentration-dependentsteady-stateequilibriuminapproximatelythirtyminutes.Measuredintracellularconcentrationof3H-Vesatolimodis5-foldhigherthantheextracellularconcentrationof3H-GS-9620usedtotreatcells.Increasesinintracellular3H-Vesatolimodconcentrationsareroughlyproportionalwithincreasingconcentrationsof3H-GS-9620[1].體內(nèi)研究SingleoraldosesofVesatolimod(GS-9620)at0.3and1mg/kginuninfectedchimpanzeesdemonstratesadose-andexposure-relatedinductionofserumIFN-α,selectcytokines/chemokines,andIFN-stimulatedgenes(ISG)intheperipheralbloodandliver.Followingoraladministrationat0.3(n=3),and1mg/kg(n=3andn=4),Vesatolimod(GS-9620)Cmaxis3.6±3.5,36.8±34.5,and55.4±81.0nM,respectively.PeakserumIFNresponsesoccurat8hpost-dose.ThemeanpeaklevelsofinducedserumIFN-αare66and479pg/mLatdosesof0.3and1mg/kg,respectively.Vesatolimod(GS-9620)treatmentinducesISGtranscriptsincludingISG15,OAS-1,MX1,IP-10(CXCL10),andI-TAC(CXCL11)inperipheralbloodmononuclearcells(PBMC)at0.3mg/kgandinbothPBMCandtheliverat1mg/kg[2].PROTOCOLCellAssay[1]Daudicellsareincubatedforindicatedtimeswithvaryingconcentrations[3H]Vesatolimod(GS-9620)(0.7μCi/mL).Cellassociatedradioactivityisextractedwithicecold80%ethanolandmeasuredusingliquidscintillationcounting.ThetotalamountofVesatolimodincellsiscalculatedfromacalibrationcurveforVesatolimod(GS-9620)massversusradioactivity.Cellvolumeismeasured[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalChimpanzee[2]Administration[2]Chimpanzeesareused.Thetrialdesignincludes4weeksofpre-studyevaluation(Day-28,-13andjustpriortofirstdose)andtwocyclesoforalVesatolimod(GS-9620)treatmenteveryotherdaythreetimesperweekfor4weekswithonecycleat1mg/kg,and,afteraoneweekrest,asecondcycleat2mg/kg.Animalsare2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEalsointenselymonitoredfor14weeksaftertreatmenttoassesstolerabilityanddurabilityofresponse.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶(hù)使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NatBiomedEng.2018Aug;2(8):578-588.?AntiviralRes.2022Jul19;205:105384.?AntiviralRes.2018May;153:39-48.?FrontMicrobiol.2018Sep19;9:2022.?ACSInfectDis.2022Feb8.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].RebbapragadaI,etal.MolecularDeterminantsofGS-9620-DependentTLR7Activation.PLoSOne.2016Jan19;11(1):e0146835.[2].LanfordRE,etal.GS-9620,anOralAgonistofToll-LikeReceptor-7,InducesProlongedSuppressionofHepatitisBVirusinChronicallyInfectedChimpanzees.Gastroenterology.2013Feb13.pii:S0016-5085(13)00169-8.[3].DTumas,etal.PreclinicalCharacterizationofGS-9620,APotentand