GIBH-130-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGIBH-130Cat.No.:HY-101860CASNo.:1252608-59-5分⼦式:C₂₀H₂₀N₆O分⼦量:360.41作⽤靶点:InterleukinRelated作⽤通路:Immunology/Inflammation储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:50mg/mL(138.73mM;Needultrasonic)H2O:<0.1mg/mL(insoluble)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.7746mL13.8731mL27.7462mL5mM0.5549mL2.7746mL5.5492mL10mM0.2775mL1.3873mL2.7746mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(6.94mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.94mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.94mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性GIBH-130有效的神经炎症抑制剂。GIBH-130作⽤于活化的⼩胶质细胞，显著抑制IL-1β分泌，IC50为3.4nM。IC50&TargetIL-1β3.4nM(IC50)体外研究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].体内研究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—您⾝边的抑制剂⼤师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.户使⽤本产品发表的科研⽂献•CellDeathDiscov.2021Jul7;7(1):175.•ResearchSquarePreprint.2021Apr.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ZhouW,etal.Microglia-BasedPhenotypicScreeningIdentifiesaNovelInhibitorofNeuroinflammationEffectiveinA