Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEHDAC6-IN-13Cat.No.:HY-151261分?式:C??H??N?O分?量:370.45作?靶點:HDAC作?通路:CellCycle/DNADamage;Epigenetics儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性HDAC6-IN-13(Compound35m)?種強效、?選擇性、具有?服活性的HDAC6抑制劑，其IC50為0.019μM。HDAC6-IN-13也抑制HDAC1、HDAC2和HDAC3，IC50分別為1.53、2.06和1.03μM。HDAC6-IN-13具有明顯的?腦屏障通透性和抗炎活性。IC50&TargetHDAC6HDAC3HDAC1HDAC20.019μM(IC50)1.03μM(IC50)1.53μM(IC50)2.06μM(IC50)體外研究HDAC6-IN-13(Compound35m)(0.1-1μM;24h)ishighlyselectivetowardHDAC6versusclassIHDACs[1].HDAC6-IN-13isaslow-onandslow-offtight-bindingHDAC6inhibitor,whileexhibitsfast-onpropertiesforHDAC1,2,and3[1].HDAC6-IN-13(5-20μM;8h)showsanti-inflammatoryactivityinvitro[1].WesternBlotAnalysis[1]CellLine:MV4?11andJ774A.1Concentration:0.1,0.2,0.5and1μMIncubationTime:24hResult:Concentration-relatedaccumulationofacetylatedtubulin(Ac-Tubulin)wasobserved,whileupregulationofacetylatedhistoneH3(AcHH3)andacetylatedhistoneH4(AcHH4)wasnotapparentevenattheconcentrationof1μM.WesternBlotAnalysis[1]1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellLine:J774A.1cellsConcentration:5,10and20μMIncubationTime:8hResult:Inhibitedthecleavageofpro-caspase1top20inadose-dependentmanner,inhibitedtheinteractionbetweenHDAC6anddynein.體內研究HDAC6-IN-13(Compound35m)(20mg/kg;p.o.andi.p.;once)displaysaremarkableinhibitioninLPS-inducedinflammationinmice[1].HDAC6-IN-13(20mg/kg;p.o.;once)showsveryhighoralbioavailability(F%=93.4%)andsignificantBBBpermeabilityinmice[1].AnimalModel:MaleC57BL/6WTmice,LPS-inducedendotoxicshockmodel[1]Dosage:20mg/kgAdministration:POandIP,immediatelyaftertheLPSinjectionResult:SignificantlydecreasedtheserumIL-1βlevelsinLPS-inducedmiceviabothipandpoadministration.AnimalModel:MaleCD-1mice[1]Dosage:5mg/kgor20mg/kgAdministration:IV(5mg/kg)orPO(20mg/kg)(PharmacokineticStudy)Result:PharmacokineticsCharacterizationofHDAC6-IN-13(Compound35m)withivandOralAdministrationa[1]PKparametersHDAC6-IN-13HDAC6-IN-13administereddose(mg/kg)ivat5mg/kgoralat20mg/kgCmax(ng/mL)4604±5515570±551t1/2(h)7.95±0.3706.80±0.145AUC0?inf(ng?h/mL)2755±39510292±1385F%n/a93.4±12.6aHDAC6-IN-13wasadministratedviaivandpo(n=3).Thebloodsamplewascollectedatdifferenttimepointsafterdosing,andtheplasmaconcentrationofHDAC6-IN-13wasdeterminedviaLC-MS/MS.Theareaundertheplasmaconcentrationversustimecurve(AUC)wascalculatedusingthelineartrapezoidalmethod.Thepharmacokineticparameterswereobtainedusingthenoncompartmentalmethod.Dataareshownasmean±SD.REFERENCES[1].YueK,etal.First-in-ClassHydrazide-BasedHDAC6SelectiveInhibitorwithPotentOralAnti-InflammatoryActivitybyAttenuating2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemENLRP3InflammasomeActivation.JMedChem.2022Sep8.McePdfHeightCaution:Producthasnotbeenfullyvalida