T6167923-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemET6167923Cat.No.:HY-19744CASNo.:2437475-16-4分?式:C??H??BrN?O?S?分?量:458.39作?靶點(diǎn):MyD88作?通路:Immunology/Inflammation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:250mg/mL(545.39mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.1815mL10.9077mL21.8155mL5mM0.4363mL2.1815mL4.3631mL10mM0.2182mL1.0908mL2.1815mL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.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(4.54mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.54mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.54mM);ClearsolutionBIOLOGICALACTIVITY?物活性T6167923?種選擇性的MyD88依賴型信號(hào)通路的抑制劑。T6167923直接與MyD88的Toll/IL1受體(TIR)結(jié)構(gòu)域結(jié)合，破壞MyD88的同?聚體形成。T6167923抑制NF-κB驅(qū)動(dòng)的葡萄球腸毒素AP(SEAP)活性，并且改抗炎活性，對(duì)IFN-γ，IL-1β，IL-6和TNF-α的IC50s分別為2.7μM，2.9μM，2.66μM和2.66μM。IC50&TargetIC50:2.7?μM(IFN-γ),2.9μM(IL-1β),2.66μM(IL-6),2.66μM(TNF-α)[2]體外研究T6167923(0-500μM;20h)inhibitsthepro-inflammatorycytokineresponseofstaphylococcalenterotoxinB(SEB)inperipheralbloodmononuclearcells[2].T6167923(10-500μM;2h)inhibitssecretedalkalinephosphataseresponse(SEAP)expressioninHEK293Tcells[2].T6167923(100μM;16h)bindstoTIRproteinandreducedtheinhibitoryeffectonMyD88-signaling[2].T6167923(1-500μM;13h)inhibitsfull-lengthMyD88homodimericformation[2].CellViabilityAssay[2]CellLine:PeripheralbloodmononuclearcellsConcentration:0-500μMIncubationTime:20hoursResult:Dose-dependentlyattenuatedtheresponseofSEBtoTNF-α,INF-γ,IL-6,andIL-1βwithIC50sof2.66,2.7,2.66and2.9μMinperipheralbloodmononuclearcells.CellViabilityAssay[2]CellLine:HEK293TcelllineConcentration:10-500μMIncubationTime:2hoursResult:Dose-dependentlyinhibitedlipo-polysaccharide(LPS)inducedMyD88-mediatedNF-kBdrivenSEAPexpressioninHEK293TcellswithIC50sintherangeof40–50μM.CellViabilityAssay[2]CellLine:HEK293TcelllineConcentration:100μM2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:16hoursResult:SpecificallytargetedMyD88anddose-denpendentlywithTIRproteintoreducedtheinhibitoryeffectofMyD88-signaling.WesternBlotAnalysis[2]CellLine:HEK293-I3AcellswithMyD88knockoutConcentration:1-500μMIncubationTime:13hoursResult:Dose-dependentlyinhibitedTIRdomain-mediateddimerizationoffull-lengthMyD88andtherecombinantTIRdomainprotein.體內(nèi)研究T6167923(0.17and1mg;i.p.once)survivesthemicefromintoxicationwithSEBandLPSinjection[2].AnimalModel:16-20week-oldBALB/cmicewithLPSpotentiationmodel[2]Dosage:0.17and1mgAdministration:Intraperitonealinjection;0.17and1mgonceResult:Dose-dependentlyshowedatherapeuticefficacyagainstSEBintoxication.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?SignalTransductTargetTher.2021Apr24;6(1):167.?JMedChem.2021May24.?CurrPharmDes.2021Jul16.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].SaqibU,etal.IdentifyingtheinhibitionofTIRproteinsinvolvedinTLRsignallingasananti-inflammatorystrategy.SARQSAREnvironRes.2018Apr;29(4):295-318.[2].OlsonMA,etal.DiscoveryofsmallmoleculeinhibitorsofMyD88-dependentsignalingpathwaysusingacomputationalscreen.SciRep.2015Sep18;5:14246.McePdfHeightCaut