INF39-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEINF39Cat.No.:HY-101868CASNo.:866028-26-4分?式:C??H??ClO?分?量:224.68作?靶點(diǎn):NOD-likeReceptor(NLR)作?通路:Immunology/Inflammation儲(chǔ)存?式:Pureform-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:100mg/mL(445.08mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM4.4508mL22.2539mL44.5077mL5mM0.8902mL4.4508mL8.9015mL10mM0.4451mL2.2254mL4.4508mL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:≥2.5mg/mL(11.13mM);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:≥2.5mg/mL(11.13mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(11.13mM);ClearsolutionBIOLOGICALACTIVITY?物活性INF39不可逆的，沒(méi)有細(xì)胞毒性的NLRP3抑制劑。體外研究INF39isabletosignificantlyinhibitATP-andnigericin-inducedIL-1βreleaseat10μM.INF39reducescaspase-1activationandpyroptosisinthemacrophages.INF39canblocknotonlyNLRP3activationbutalsotheNF-κBpathway.INF39potentiallyreactswithCys-SHresiduesintheactivesiteofcysteineproteasecaspase-1,butdoesnotdirectlytargetcaspase-1activity.INF39isabletoreducethesteadystate(orbasal)BRETsignalofNLRP3withoutaffectingtheviabilityofcells,meaningthatitcaninterferewiththebasalNLRP3conformation.INF39doesnotblocktheinitialconformationalchangessufferedbyNLRP3uponsensingthedecreaseofintracellularK+;however,itaffectsasecondstepofNLRP3conformationalchangethatcouldberelatedwiththeATPaseactivityofthereceptorandbeindependentofthedecreaseofintracellularK+.INF39reachestheintestinalepitheliumwithoutundergoingchemicalmodifications.Afterabsorptionintoepithelialcells,itislikelytoactlocallyatthemucosalepitheliallevel[1].體內(nèi)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?邊的抑制劑?師www.MedChemEand1%methylcellulose,respectively,andadministeredinavolumeof0.2mL/rat.DNBS-untreatedanimals(controlgroup)andDNBS-treatedrats(colitisgroup)receiveddrugvehicletoserveascontrols.Bodyweightismonitoreddailystartingfromtheonsetofdrugtreatments[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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