A2AAR-HDAC-IN-1-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEA2AAR/HDAC-IN-1Cat.No.:HY-143324CASNo.:2767560-51-8分?式:C??H??N?O?分?量:439.47作?靶點:HDAC;AdenosineReceptor作?通路:CellCycle/DNADamage;Epigenetics;GPCR/GProtein儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物A2AAR/HDAC-IN-1(compound14c)?種?服有效且平衡的A2AAR/HDAC雙抑制劑，其對A2AAR的Ki為163.5nM,對HDAC1的IC50活性anticancer)活性。IC50&A2ARA1ARhA2BTarget163.5±14nM(Ki)503.3±14nM(Ki)>10000nM(Ki)HDAC1HDAC2HDAC3145.3±12nM(IC50)240.2±19nM(IC50)443.5±27nM(IC50)HDAC8>10000nM(IC50)體外A2AAR/HDAC-IN-1(compound14c)(0-100μM,72h)showsanti-proliferativeactivitiesagainstcoloncancercelllines,CT26andMC38[研究A2AAR/HDAC-IN-1(0-5μM,24h)increaseshistoneacetylation[1].A2AAR/HDAC-IN-1showsmoderateselectivityagainstA1AR(3-fold)andnosignificantbindingforA2BARandA3AR[1].CellProliferationAssay[1]CellLine:Coloncancercelllines(CT26andMC38)Concentration:0-100μMIncubationTime:72h1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResult:DisplayedgoodcytotoxicityinCT26andMC38cells,withGI50valuesof0.29±0.03μMand0.38±0.03μM,respecWesternBlotAnalysis[1]CellLine:MC38mousecoloncancercellsConcentration:0,0.1,1,and5μMIncubationTime:24hResult:IncreasedhistoneH3andH4acetylationinaconcentration-dependentmanner.體內(nèi)研A2AAR/HDAC-IN-1(compound14c)(30or60mg/kg,IP,twicedailyfor9days)showspotentanti-tumoreffectsinthemouseMC38xeno究A2AAR/HDAC-IN-1(90mg/kg,bid;150mg/kg,qd;Oralgavage,for15days)showsweaktumorsuppression[1].A2AAR/HDAC-IN-1(5mg/kg,IV;20mg/kgPOorIP;once)showsanoverallfavorablepharmacokineticprofile[1].AnimalModel:MaleICRmice(6-8weeks,~25gbodyweight,MC38coloncancermodel)[1]Dosage:30or60mg/kgAdministration:IP,twicedailyfor9daysResult:Significantlyinhibitedtumorgrowthatadosageof30mg/kg(ip,bid),withatumorgrowthinhibition(TGI)rateof68%increasedto85%.AnimalModel:MaleICRmice(6-8weeks,~25gbodyweight,MC38coloncancermodel)[1]Dosage:90mg/kg,bid;150mg/kg,qdAdministration:Oralgavage,twicedaily(90mg/kg)ordaily(150mg/kg),for15daysResult:Showedonlyweaktumorsuppressionevenatadoseof90mg/kg(po,bid),withinhibitionratesof44%.AnimalModel:MaleICRmice(6-8weeks,~25gbodyweight)[1]Dosage:5mg/kg(IV)and20mg/kg(PO,IP)Administration:Orally,IP,orIV;once(Pharmacokinetic2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnalysis)Result:PharmacokineticParametersofREFERENCESA2AAR/HDAC-IN-1inmaleICRmice[1].[1].ZhangJ,etal.Dual-actingantitumoragentstargetingtheA2Aadenosinereceptorandhis(furan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-aminederivatives.EurJMedChem.2022Jun5;23PKParametersMcePdfHeightpo(20mg/kg)iv(5mg/kg)ip(20mg/kg)Kel(h-1)0.390±0.1871.820±0.3000.844±0.021t1/2(h)2.24±1.160.389±0.0700.83±0.02Tmax(h)0.333±0.140.25±Caution:Producthasnotbeenfullyvalidatedformedicalapplications.0.00CmaxForresearchuseonly.(ng/mL)3417±Tel:400-820-3792ax-mail:tech@MedChemE1