Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESHP2/HDAC-IN-1Cat.No.:HY-151464分?式:C??H??Cl?N?O?分?量:660.59作?靶點:SHP2;Phosphatase;HDAC作?通路:ProteinTyrosineKinase/RTK;MetabolicEnzyme/Protease;CellCycle/DNADamage;Epigenetics儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性SHP2/HDAC-IN-1?種變構(gòu)的SHP2/HDAC雙重抑制劑，IC50值分別為20.4nM(SHP2)和25.3nM(HDAC1)。SHP2/HDAC-IN-1通過激活T細胞、增強抗原呈遞功能和促進細胞因?分泌來觸發(fā)抗腫瘤免疫反應。SHP2/HDAC-IN-1可?于癌癥的免疫治療研究。IC50&TargetHDAC1HDAC2HDAC3HDAC625nM(IC50)79nM(IC50)233nM(IC50)27nM(IC50)SHP220.4nM(IC50)體外研究SHP2/HDAC-IN-1(compound8t,0-10μMapproximately,72h)inhibitstheproliferationofBxPC-3,SW1990,AsPC-1andMV4-11cells[1].SHP2/HDAC-IN-1(0.25-1μM,24h)increasestheacetylationofα-tubulinandhistoneH3inMV4-11cells[1].SHP2/HDAC-IN-1(0.25μM,24h)inhibitscellcycleprogressionintheG1phaseofMV4-11cells[1].SHP2/HDAC-IN-1(0.25and0.5μM,24h)decreasesthemitochondrialmembranepotentialandactivatscaspase-3[1].SHP2/HDAC-IN-1(2h)showsgoodstabilityininmouselivermicrosome[1].CellProliferationAssay[1]CellLine:Pancreaticcarcinoma(BxPC-3,SW1990,andAsPC-1),acutemonocyticleukemia(MV4-11)Concentration:0-10μMapproximately1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:72hResult:InhibitedcellproliferationwithIC50srangeof0.07μM-3.92μM.WesternBlotAnalysis[1]CellLine:MV4-11cellsConcentration:0.25,0.5,1μMIncubationTime:24hResult:Increasedtheacetylationofα-tubulinandhistoneH3.InhibitedthephosphorylationlevelofERK.體內(nèi)研究SHP2/HDAC-IN-1(compound8t,40mg/kg,p.o.)inhibitstumorgrowthinMV4-11and4T1tumor-bearingxenograftmice[1].SHP2/HDAC-IN-1(20mg/kgp.o.,1mg/kgi.v.)exhibitsgoodmaximumplasmaconcentrationsinrats[1].AnimalModel:MV4-11tumor-bearingxenograftmice[1]Dosage:40mg/kgAdministration:Oraladminstration(p.o.),everydayfor20consecutivedays.Result:Delayedtumorprogressionwithatumorgrowthinhibitionrate(TGI%)valueof64.0%,withnoobvioussignsoftoxicity.AnimalModel:4T1murinebreastcancermodel[1]Dosage:40mg/kgAdministration:Oraladminstration(p.o.),everydayfor12consecutivedays.Result:SignificantlydecreasedtumorburdenwithaTGIvalueof72%.IncreasedtheproportionsofCD4+TcellsandCD8+Tcellsinthespleen.EnhancedtheproportionofmDCsinlymphnodes.AnimalModel:MaleSprague-Dawley(SD)rats(Pharmacokineticassay)[1]Dosage:20mg/kgp.o.,1mg/kgi.v.Administration:Oraladminstration(p.o.)orintravenousinjection(i.v.)Result:PharmacokineticprofileofSHP2/HDAC-IN-1(compound8t).dose(mg/kg)T1/2(h)Cmax(ng/mL)Cl(mL/h/kg)F(%)20(p.o.)5.32183521.4212/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE(i.v.)6.153517326REFERENCES[1].MengLiu,etal.DiscoveryofNovelSrcHomology-2Domain-ContainingPhosphatase2andHistoneDeacetylaseDualInhibitorswithPotentAntitumorEfficacyandEnhancedAntitumorImmunity.JMedChem.2022Sep22;65(18):12200-12218.McePdfHeightCaution:Producthasnotbeenfullyvalid