DDO-2728-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEDDO-2728Cat.No.:HY-155489分子式: C₂₈H₁₇F₃N₄O₇分子量: 578.45作用靶点: Anaplasticlymphomakinase(ALK);Apoptosis作用通路: ProteinTyrosineKinase/RTK;Apoptosis储存方式: PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性DDO-2728(化合物19)是一种选择性AlkBhomologue5(ALKBH5)抑制剂，其IC50为2.97μM。DDO-2728增加N6methyladenosine(m6A)修饰的丰度，诱导细胞凋亡和细胞周期阻滞。DDO-2728在MV4−11异种移植模型中抑制肿瘤生长且具有良好的安全性，显示出靶向ALKBH5在癌症研究中的潜力[1]。IC50&TargetAlkBhomologue5(ALKBH5)IC50:2.97μM[1]体外研究DDO-2728(0-40μM,48h)increasesm6AmethylationlevelsintheMOLM-13,HEK293andMV4−11cellsoveraconcentrationgradient[1].DDO-2728(0.01-100μM,72h)inhibitstheproliferationofMOLM-13andMV4−11cellswithIC50sof0.45and1.2μMrespectively,andshowesarelativelyweaktoxicityinHEK293andHUVECs[1].DDO-2728(20μM,48h)significantlyarreststhecellcycleofMOLM-13andMV4−11cellsattheG1/Mphase[1].DDO-2728(5,10μM,48h)concentration-dependentlyinducescellapoptosisofMV4−11andMOLM-13cells[1].DDO-2728(20μM,24h)decreasesthehalf-livesofTACC3mRNAinMOLM-13andMV4−11cells[1].DDO-2728(0-10μM,48h)significantlyreducestheabundanceofTACC3andc-MycinMOLM-13andMV4−11cellsatbothmRNAandproteinlevels[1].1.19MetabolicStabilityinRatandHumanPlasmaandLiverMicrosomes[1]SpeciesPlasmaT1/2(min)MicrosomeT1/2(min)MicrosomeCL(μL/min/mg)Human6244303.2Rat25113.8100.4CellProliferationAssay[1]1/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemECellLine:MOLM-13,MV4-11,HEK293,HUVECConcentration:0.01-100μMIncubationTime:72hResult:InhibitedtheproliferationofMOLM-13andMV4−11cellswithIC50sof0.45and1.2μMrespectively,didn'tshowvisualcytotoxicityinHEK293andHUVECsunder1μM.ApoptosisAnalysis[1]CellLine:MOLM-13,MV4-11Concentration:0,5,10μMIncubationTime:48hResult:InducedcellapoptosisofMV4−11andMOLM-13cellsconcentration-dependently,apoptosisrateforMV4−11increasedfrom7.17%to55.4%,apoptosisrateforMOLM-13increasedfrom6.49%to31.5%.CellCycleAnalysis[1]CellLine:MOLM-13,MV4-11Concentration:20μMIncubationTime:48hResult:ArrestedthecellcycleofMOLM-13andMV4−11cellsattheG1/MphaseasnoG2/Mphasecellsexist.体内研究DDO-2728(10-40mg/kg,i.p.,dailyfor14d)effectivelyinhibitstumorgrowthinMV4−11xenograftnudemice.[1].1.19PharmacokineticParametersofDDO-2728inRats[1]ParameterRat(i.v.,2mg/kg)Rat(i.p.,10mg/kg)T1/2(min)36.7±3.2148.3±4.6Cmax(ng/mL)13388.3±784.52337.5±295.7Tmax(min)30AUC0-∞(min·μg/mL)404.3±58.6349.1±26.1Vz_F_obs(mL/kg)263.6±17.56177.6±650.2Cl_F_obs(mL/min/kg)5.0±0.528.8±2.2MRT(min)77.8±15.5168.2±1.2F(%)17.3AnimalModel:MV4−11xenograftnudemice[1]Dosage:10,20,and40mg/kgAdministration:Intraperitonealinjection(i.p.)dailyfor14dResult:Inhibitedtumorgrowthsignificantlyevenataconcentrationof10mg/kg.Nosignificant2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEchangeintheweightofthemiceandthemainorgansduringthetreatment,theorganweightoftestgroupmicewasthesameasvehiclegroup,noobviousinjurydamagewasobservedintheHEstainingimagesoforgantissues.REFERENCESZheng-YuJiang,etal.DiscoveryofPyrazolo[1,5-a]pyrimidineDerivativeasaNovelandSelectiveALKBH5InhibitorfortheTreatmentofAML.JournalofMedicinalChemistry.2023，ArticleASAP.McePdfHeightCaution:Producthasn