Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEResatorvidCat.No.:HY-11109CASNo.:243984-11-4分?式:C??H??ClFNO?S分?量:361.82作?靶點:Toll-likeReceptor(TLR);TNFReceptor;InterleukinRelated;Autophagy作?通路:Immunology/Inflammation;Apoptosis;Autophagy儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:100mg/mL(276.38mM;Needultrasonic)掃描?維碼，H2O:<0.1mg/mL(insoluble)運?溶解?案計算器獲得適合您實驗體系的溶解?案MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.7638mL13.8190mL27.6381mL5mM0.5528mL2.7638mL5.5276mL10mM0.2764mL1.3819mL2.7638mL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，并請注意儲備液的保存?式和期限。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：1%DMSO99%saline2.Solubility:0.5mg/mL(1.38mM);Suspendedsolution;Needultrasonic請依序添加每種溶劑：10%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.75mg/mL(7.60mM);Clearsolution此?案可獲得≥2.75mg/mL(7.60mM，飽和度未知)的澄溶液。1/4www.MedChemEwww.MedChemE以1mL?作液為例，取100μL27.5mg/mL的澄DMSO儲備液加到400μLPEG300中，混合均勻；向上述3.體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。請依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:2.75mg/mL(7.60mM);Suspendedsolution;Needultrasonic此?案可獲得2.75mg/mL(7.60mM)的均勻懸濁液，懸濁液可?于?服和腹腔注射。以1mL?作液為例，取100μL27.5mg/mL的澄DMSO儲備液加到900μL20%的SBE-β-CD?理鹽??溶4.液中，混合均勻。請依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥2.75mg/mL(7.60mM);Clearsolution此?案可獲得≥2.75mg/mL(7.60mM，飽和度未知)的澄溶液，此?案不適?于實驗周期在半個?以上的實驗。5.以1mL?作液為例，取100μL27.5mg/mL的澄請依序添加每種溶劑：10%DMSO90%salineDMSO儲備液加到900μL??油中，混合均勻。6.Solubility:5mg/mL(13.82mM);Suspendedsolution;Needultrasonic請依序添加每種溶劑：5%DMSO40%PEG3005%Tween-8050%saline7.Solubility:5.5mg/mL(15.20mM);Suspendedsolution;Needultrasonic請依序添加每種溶劑：5%DMSO95%(20%SBE-β-CDinsaline)8.Solubility:5.5mg/mL(15.20mM);Suspendedsolution;Needultrasonic請依序添加每種溶劑：5%DMSO95%salineSolubility:2.5mg/mL(6.91mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Resatorvid(TAK-242)?種選擇性的TLR4信號傳導抑制劑。Resatorvid抑制NO，TNF-α和IL-6的產(chǎn)?，其IC50值分別為1.8nM，1.9nM，1.3nM。Resatorvid下調(diào)TLR4下游信號分?MyD88和TRIF的表達。Resatorvid抑制?噬(autophagy)，并在各種炎癥性疾病中起關鍵作?。IC50&TargetTLR4TNF-RIL-61.9nM(IC50)1.3nM(IC50)體外研究ResatorvidsuppressestheproductionofNO,TNF-α,andIL-6fromLPS-stimulatedhumanperipheralbloodmononuclearcells(PBMCs)atIC50valuesfrom11to33nM[1].Resatorvid(1-100nM;4hours)inhibitsmRNAexpressionofIL-6andTNF-αinducedbyLPSandIFN-γinRAW264.7cells[1].Resatorvid(1-100nM;15minutes;PBMCscells)markedlyinhibitstheLPS-inducedphosphorylationofextracellularsignal-regulatedkinase1/2(Erk1/2),p38,andJNK/SAPKaswellasdegradationofIκBβataconcentrationof100nM[1].RT-PCR[1]CellLine:RAW264.7cellsConcentration:1nM,10nM,100nMIncubationTime:4hours2/4www.MedChemEwww.MedChemEResult:TNF-αandIL-6mRNAexpressionlevelswereclearlysuppressedatconcentrationsof10to100nM.WesternBlotAnalysis[1]CellLine:PBMCscellsConcentration:1nM,10nM,100nMIncubationTime:15minutesResult:Thephosphorylationofmitogen-activatedproteinkinasesinducedbyLPSwasalsoinhibitedinaconcentration-dependentmanner.體內(nèi)研究Resatorvid(TAK-242;3?mg/kg;intraperitonealinjection;for2days;maleC57BL/6mice)pretreatmentmarkedlyandsignificantlyreversestheLPS-inducedbodyweightloss,TAmuscleloss,andmusclestrengthloss.TAK-242reversestheLPS-inducedshrinkageofmusclefibresandincreasestheinterstitialspace.TAK-242blockssystemiccataboliccytokinereleaseandskeletalmuscleproteolysisinLPS-administeredmice[3].AnimalModel:MaleC57BL/6mice(8-12weeksofage)treatedwithlipopolysaccharide(LPS)[3]Dosage:3?mg/kgAdministration:Intraperitonealinjection;for2daysResult:PretreatmentofmicereducedorreversedallthedetrimentaleffectsofLPS.戶使?本產(chǎn)品發(fā)表的科研?獻?Gut.2020Oct29;gutjnl-2020-320777.?CellHostMicrobe.2021Feb10;29(2):222-235.e4.?NatCommun.2019Mar4;10(1):1015.?BasicResCardiol.2017Jan;112(1):9.?Biomaterials.2020May;241:119852.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].IiM,etal.Anovelcyclohexenederivative,ethyl(6R)-6-[N-(2-Chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate(TAK-242),selectivelyinhibitstoll-likereceptor4-mediatedcytokineproductionthroughsuppressionofintracellularsignaling.[2].YamadaM,etal.Discoveryofnovelandpotentsmall-moleculeinhibitorsofNOandcytokineproductionasantisepsisagents:synthesisandbiologicalactivityofalkyl6-(N-substitutedsulfamoyl)cyclohex-1-ene-1-carboxylate.JMedChem.2005Nov17;48(23):7457-67.3/4www.MedChemEwww.MedChemE[3].YukoOno,etal.TAK-242,aSpecificInhibitorofToll-likeReceptor4Signalling,PreventsEndotoxemia-InducedSkeletalMuscleWastinginMice.SciRep.2020Jan20;10(1):694.McePdfHeight關注MCE中