INF39-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEINF39Cat.No.:HY-101868CASNo.:866028-26-4分⼦式:C₁₂H₁₃ClO₂分⼦量:224.68作⽤靶点:NOD-likeReceptor(NLR)作⽤通路:Immunology/Inflammation储存⽅式:Pureform-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(445.08mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM4.4508mL22.2539mL44.5077mL5mM0.8902mL4.4508mL8.9015mL10mM0.4451mL2.2254mL4.4508mL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%salineSolubility:≥2.5mg/mL(11.13mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(11.13mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(11.13mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性INF39不可逆的，没有细胞毒性的NLRP3抑制剂。体外研究INF39isabletosignificantlyinhibitATP-andnigericin-inducedIL-1βreleaseat10μM.INF39reducescaspase-1activationandpyroptosisinthemacrophages.INF39canblocknotonlyNLRP3activationbutalsotheNF-κBpathway.INF39potentiallyreactswithCys-SHresiduesintheactivesiteofcysteineproteasecaspase-1,butdoesnotdirectlytargetcaspase-1activity.INF39isabletoreducethesteadystate(orbasal)BRETsignalofNLRP3withoutaffectingtheviabilityofcells,meaningthatitcaninterferewiththebasalNLRP3conformation.INF39doesnotblocktheinitialconformationalchangessufferedbyNLRP3uponsensingthedecreaseofintracellularK+;however,itaffectsasecondstepofNLRP3conformationalchangethatcouldberelatedwiththeATPaseactivityofthereceptorandbeindependentofthedecreaseofintracellularK+.INF39reachestheintestinalepitheliumwithoutundergoingchemicalmodifications.Afterabsorptionintoepithelialcells,itislikelytoactlocallyatthemucosalepitheliallevel[1].体内研究OraladministrationofINF39reducessystemicandcolonicinflammationinratstreatedwith2,4-dinitrobenzenesulfonicacid.SignificantincrementsofbodyweightareobservedininflamedratsundertreatmentwithINF39(12.5,25,and50mg/kg).TreatmentwithDNBSresultsinasignificantincrementofspleenweight(+39.3%).SuchanincreaseissignificantlyreducedbyadministrationofINF39(+2.2,+4.3and+4.8%at12.5,25,50mg/kg,respectively).TheinhibitionofNLRP3inflammasomecomplexwithINF39dose-dependentlyattenuatesthedecreaseincoloniclength(−19,−13and−8%at12.5,25,50mg/kg,respectively).RatstreatedwithINF39displaysasignificantreductionofmacroscopicdamagescore(4.7at12.5mg/kg,3.1at25mg/kg,and2.8at50mg/kg).OraladministrationofINF39reducescolonicmyeloperoxidase,IL-1β,andTNFLevelsinDNBS-treatedrats[1].PROTOCOLKinaseAssay[1]INF39(100μMfinalconcentration,2%DMSO)isaddedtowellscontainingimmobilizedNALP3proteinandpreincubatedfor55minat37°Ctomimicnormalexperimentaltime(15minpreincubation+40minincubationwithATP);inthecontrolwellsamixtureofbufferandDMSOisadded.Afterthepreincubationtimethewellsareishedthreetimeswithreactionbuffer,andATP(250μM)isaddedfor40minat37°C.ADPformationismeasuredwithADP-Glo-Assay[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalRats:Administration[1]DNBS-untreatedandDNBStreatedanimalsareassignedtothefollowingtreatmentgroups:INF39(12.5,25,50mg/kg/day)ordexamethasone(DEX,1mg/kg/day).INF39anddexamethasonearesuspendedinoliveoil2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEand1%methylcellulose,respectively,andadministeredinavolumeof0.2mL/rat.DNBS-untreatedanimals(controlgroup)andDNBS-treatedrats(colitisgroup)receiveddrugvehicletoserveascontrols.Bodyweightismonitoreddailystartingfromtheonsetofdrugtreatments[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•Phytomedicine.17November2021,153860.•AmJChinMed.2020;48(7):1693-1713.•IntImmunopharmacol.September2022,108910.•IntImmunopharmacol.2022Jan10;104:108443.•AmJTranslRes.2019Jul15;11(7):3992-4009.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].CoccoM,etal.DevelopmentofanAcrylateDerivativeTargetingtheNLRP3InflammasomefortheTreatmentofInflammatoryBowelDisease.JMedC