CDK-HDAC-IN-2-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECDK/HDAC-IN-2Cat.No.:HY-146276CASNo.:2580938-58-3分?式:C??H??Cl?N?O?分?量:523.37作?靶點(diǎn):HDAC;CDK;Apoptosis作?通路:CellCycle/DNADamage;Epigenetics;Apoptosis儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性CDK/HDAC-IN-2?種有效的HDAC/CDK雙重抑制劑，對(duì)于HDAC1,HDAC2,HDAC3,HDAC6,8,CDK1,CDK2,CDK4,6,7,IC50分別為6.4,0.25,45,>1000,8.63,0.30,>1000nM。CDK/HDAC-IN-2顯?出優(yōu)異的抗增殖活性。CDK/HDAC-IN-2誘導(dǎo)細(xì)胞凋亡(apoptosis)和細(xì)胞周期停滯在G2/M期。CDK/HDAC-IN-2顯?出強(qiáng)?的抗腫瘤功效[1]。IC50&TargetHDAC1HDAC2HDAC3HDAC66.4nM(IC50)0.25nM(IC50)45nM(IC50)>1000nM(IC50)HDAC8CDK1CDK2CDK4>1000nM(IC50)8.63nM(IC50)0.30μM(IC50)>1000nM(IC50)CDK6CDK7>1000nM(IC50)>1000nM(IC50)體外研究CDK/HDAC-IN-2(compound7c)showsantiproliferativeactivitywithIC50sof0.71,1.20,1.83,4.19,7.76,4.47μMforHCT116,A375,Hela,H460,SMMC7721,NIH3T3cells,respectively[1].CDK/HDAC-IN-2(24h)showsanti-migrationabilityinA375andH460cells[1].CDK/HDAC-IN-2(0.5,1,2μM)inducesapoptosisandcellcyclearrestatG2/Mphase[1].CDK/HDAC-IN-2acceleratesintracellularROSaccumulation,leadingtocancercelldeath[1].CellCycleAnalysis[1]CellLine:A375,HCT116,H460,Helacells1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEConcentration:0.5,1,2μMIncubationTime:24hResult:InducedcellcyclearrestatG2/Mphase.ApoptosisAnalysis[1]CellLine:A375,HCT116,H460,HelacellsConcentration:0.5,1,2μMIncubationTime:48hResult:InducedcellapoptosiswiththeapoptosisratesofA375,HCT116cellsof97.22%,60.6%,respectively.體內(nèi)研究CDK/HDAC-IN-2(12.5,25mg/kg;IP;oncedailyfor21days)showsantitumorefficacyintheHCT116xenograftmodel(TGI=51.0%)[1].PharmacokineticParametersofCDK/HDAC-IN-2inICRmalemice[1].compound7cDose(mg/kg)20administrationi.p.t1/2(h)2.61Tmax(h)2.00Cmax(h)7570AUC0-∞(ngh/mL)30700MRT0-∞(ngh/mL)3.31F(%)63.6ICRmalemice;20mg/kg,i.p.[1].AnimalModel:ICRmalemice[1]Dosage:20mg/kgAdministration:IPResult:ShowedgoodPharmacokineticparameterswithbioavailabilityofF=63.6%.AnimalModel:5-6weeks,BALB/cfemalemice(HCT116xenograftnudemicemodels)[1]Dosage:12.5,25mg/kgAdministration:IP,oncedailyfor21daysResult:EffectivelyinhibitedthegrowthofHCT116xenografttumorstumorgrowthinhibitions(TGI)at12.5and25mg/kgof37.0%and51.0%,respectively.REFERENCES[1].ChengC,etal.Discoveryofnovelcyclin-dependentkinase(CDK)andhistonedeacetylase(HDAC)dualinhibitorswithpotentinvitroandinvivoanticanceractivity.EurJMedChem.2020Mar1;189:112073.McePdfHeight2/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECaution:Producthasnotbeenfullyvalidatedformedicala