MLT-943-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMLT-943Cat.No.:HY-134820CASNo.:1832576-04-1分?式:C??H??ClF?N?O?分?量:414.77作?靶點(diǎn):MALT1作?通路:MetabolicEnzyme/Protease;NF-κB儲存?式:Powder-20°C3yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:250mg/mL(602.74mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.4110mL12.0549mL24.1097mL5mM0.4822mL2.4110mL4.8219mL10mM0.2411mL1.2055mL2.4110mL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?jiān)?個?內(nèi)使?，-20°C儲存時，請?jiān)?個?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥?式選擇適當(dāng)?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(shí)驗(yàn)結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，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(5.01mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoil1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(5.01mM);ClearsolutionBIOLOGICALACTIVITY?物活性MLT-943?種有效的、選擇性的、?服活性的MALT1protease抑制劑。MLT-943可抑制PBMC或全?中IL-2的分泌，PBMC中抑制的IC50值為0.07~0.09μM，全?中抑制的IC50值為0.6~0.8μM)。MLT-943具有抗炎活性，可?于FcgR介導(dǎo)的炎癥研究。體外研究MLT-943showsahighpotencyandselectivityinvitro.MLT-943inhibitsstimulatedIL-2secretioninPBMCorinwholebloodwithasimilarIC50acrossspecies(0.07-0.09μMinPBMC,0.6-0.8μMinwholeblood)[1].體內(nèi)研究MLT-943(oralgavage;10mg/kg;QD)prophylactictreatmentintheratcollagen-inducedarthritismodelsuppressesanti-collagenantibodyproduction,fullypreventspawswelling,andnormalizesjointhistologyscoresinratmodel[1].MLT-943(oralgavage;5mg/kg;QD;10consecutivedays)effectivelyinhibitsMALT1proteaseactivityandresultsinaprogressivereductioninthefrequencyofFoxp3+CD25+TregcellsincirculatingCD4+Tcells,whichwasmaximalafter7daysoftreatment.AndDiscontinuationofMLT-943treatmentafterday10leadstoTregfrequencyprogressivelyreturningtotheiroriginalvalueswithin4days.SuboptimaldosesofMLT-943(0.1and0.5mg/kgQD;p.o.)doesnotimpacttheTregfrequency[1].MLT-943(oralgavage;0,5,20or80mg/kg/day;4-13weeks)causesareductioninTregandanincreaseintotalTcellcounts,inboth4-and13-weekrattoxicitystudiesatalldoselevels.Whilea4-Longertreatmentinducessevereimmune-mediatedpathologyinmultipleorgans,withclinicalonsetstartingaroundweek9inrat[1].MLT-943(p.o.admistration;3mg/kg;singledose)exhibitsagoodPKparametersinvivo.TheCmaxvaluesare0.7nMand0.5nM,respectivelyinratandmice,respectively.AndtheF%are86%and50%inratandmice,respective[1].Fori.v.admistrationthecompoundisformedinNMP:PEG200(30/70);Forp.o.admistrationsolutionisformedinMC:Tween80:Water(0.5:0.5:99)solution(Sourcedfromliterature,forreferenceonly)[1].AnimalModel:Na?verats[1]Dosage:5mg/kgAdministration:Oralgavage;5mg/kg,10consecutivedaysor0.1mg/kgMLT-943Result:Inducedasevereimmune-mediatedpathologyafteraprolongedtreatmentREFERENCES[1].KeaMartin,etal.PharmacologicalInhibitionofMALT1ProteaseLeadstoaProgressiveIPEX-LikePathology.FrontImmunol[2].JeanQuancard,etal.OptimizationoftheInVivoPotencyofPyrazolopyrimidineMALT1ProteaseInhibitorsbyReducingMetabolismandIncreasingPotencyinWholeBlood.JMedChem.2020Dec10;63(23):14594-14608.McePdfHeightCaution:Producthasno