Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGIBH-130Cat.No.:HY-101860CASNo.:1252608-59-5分?式:C??H??N?O分?量:360.41作?靶點(diǎn):InterleukinRelated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:50mg/mL(138.73mM;Needultrasonic)H2O:<0.1mg/mL(insoluble)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.7746mL13.8731mL27.7462mL5mM0.5549mL2.7746mL5.5492mL10mM0.2775mL1.3873mL2.7746mL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%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(6.94mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.94mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.94mM);ClearsolutionBIOLOGICALACTIVITY?物活性GIBH-130有效的神經(jīng)炎癥抑制劑。GIBH-130作?于活化的?膠質(zhì)細(xì)胞，顯著抑制IL-1β分泌，IC50為3.4nM。IC50&TargetIL-1β3.4nM(IC50)體外研究GIBH-130isanovelantineuroinflammatoryagentthatisidentifiedthroughmicroglia-basedphenotypicscreenings.GIBH-130(IC503.4nM)isidentifiedinscreeningsasoneofthemosteffectiveinhibitorswithanacceptablehalf-life.PretreatmentofmicrogliawithGIBH-130significantlyreducestheproductionofthesefactorsinresponsetoLipopolysaccharides(LPS)stimulation,andtheextentofthereductionisdependentontheconcentrationsofGIBH-130.TheIC50valuesofGIBH-130forNOandTNF-αinhibitionare46.24and40.82μM,respectively.Notably,pretreatmentwithGIBH-130significantlysuppressestheIL-1βsecretionbyactivatedmicroglia(IC50=3.4nM).TheinhibitoryefficiencyofGIBH-130at20nMiscomparableto20μMminocyclineagainstIL-1βrelease.IL-1βisoneofthemajorcytokinesduringneuroinflammatoryprogressionofAD.So,itismeaningfultoexplaintheselectivityofGIBH-130againstIL-1β(IC50value3.4nM)overNOandTNF-α(IC50value46.24and40.82μM,respectively)[1].體內(nèi)研究GIBH-130exhibitscomparableinvivoefficacyofcognitiveimpairmentrelieftodonepezilandmemantinerespectivelyinbothβamyloid-inducedandAPP/PS1doubletransgenicAlzheimer’smurinemodelsatasubstantiallylowerdose(0.25mg/kg).ThepharmacokineticpropertiesofGIBH-130areassessedinSprague-Dawleyrats.AsapotentialdrugcandidatetargetinginCNS,GIBH-130isfoundtobeorallybioavailableinrats,with74.91%bioavailabilityand4.32hhalf-life.Inaddition,GIBH-130displaysgoodpenetrationabilityacrossblood-brainbarrier(AUCBrain/Plasma=0.21)[1].PROTOCOLCellAssay[1]ThemurinemicroglialcelllineN9(N9cells)areculturedinDMEMsupplementedwith10%FBS,1mMsodiumpyruvate,100U/mLpenicillin,and100μg/mLstreptomycin.AllculturesaremaintainedinahumidifiedCO2incubatorat37°Cand5%CO2.StockN9cellsarepassaged2-3times/weekwitha1:4splitratioandusedwithin8passages.N9cells(5×104cells/well)areplatedinto96-wellmicrotiterplates,followedbythetreatmentofMinocycline(20μM)orvariousconcentrationsoftheGIBH-130(25,50,and100μM)for18h.TheNOproductionisstimulatedbyincubationwithLPS(1μg/mL)for48h.ThelevelsofNOintheculturemediumaremeasuredusingthenitricoxidedetectionkit[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalRats[1]Administration[1]Sprague-Dawley(SD)rats(halfmaleandhalffemale,250–270g)areused.RatsexposedtoAβ25-35receivedoral(p.o.)GIBH-130(0.0022,0.02,or0.18mg/kg),Donepezilhydrochloride(0.9mg/kg),Memantinehydrochloride(1.8mg/kg)ordistilledwaterviagavageaftertheAβ25-35injection.Thesham-operatedgroupreceiveap.o.administrationofdistilledwater(n=10pergroup).Allcompoundsaresystemicallyadministeredinavolumeof0.01mLpergbodyweightoncedailyafterthedayofsurgeryuntiltheendofthebehavioraltesting.Thebehavioraltestsstarted8daysaftertheAβ25-35injectionandareperformedsequentially.Mice[1]APP/PS1transgenicmice(halfmaleandhalffemale,14weeksage)andage-and-strained-matchedwildtypemice(C57BL/6J)areused.APP/PS1transgenicmicearerandomlydividedintosixgroups:modelgroup,GIBH-1300.0031,0.028,and0.25mg/kggroup,Donepezilhydrochloride1.3mg/kggroup,andMemantinehydrochloride2.6mg/kggroup(n=10pergroup).C57BL/6Jmiceareusedasnormalcontrolgroup(n=10).ThedosesofGIBH-130andthepositivedrugsusedinthismousemodelareequivalenttotheratmodel.Allmicereceiveoraladministrationat15weeksofageandcontinuouslyfor25weeksuntiltheendofthebehavioraltests.Themodelgroupandnormalcontrolgroupreceivethesamevolumeofdistilledwater(0.01mLpergbodyweight).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?CellDeathDiscov.2021Jul7;7(1):175.?ResearchSquarePreprint.2021Apr.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ZhouW,etal.Microglia-BasedPhenotypicScreeningIdentifiesaNovelInhibitorofNeuroinflammationEffectiveinA