Mocetinostat-MGCD0103-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMocetinostatCat.No.:HY-12164CASNo.:726169-73-9Synonyms:MGCD0103分⼦式:C₂₃H₂₀N₆O分⼦量:396.44作⽤靶点:HDAC;Autophagy;Apoptosis作⽤通路:CellCycle/DNADamage;Epigenetics;Autophagy;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:50mg/mL(126.12mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.5224mL12.6122mL25.2245mL5mM0.5045mL2.5224mL5.0449mL10mM0.2522mL1.2612mL2.5224mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.08mg/mL(5.25mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(5.25mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Mocetinostat(MGCD0103)⼀种有效，可⼝服和同种型选择性的HDAC(ClassI/IV)抑制剂，抑制HDAC1，HDAC2，HDAC3和HDAC11的IC50分别为0.15，0.29，1.66和0.59μM。Mocetinostat对HDAC4，HDAC5，HDAC6，HDAC7或HDAC8没有抑制作⽤。IC50&TargetHDAC1HDAC2HDAC11HDAC30.15μM(IC50)0.29μM(IC50)0.59μM(IC50)1.66μM(IC50)体外研究Mocetinostatisapotent,orallyactiveandisotype-selectiveHDAC(ClassI/IV)inhibitorwithIC50sof0.15,0.29,1.66and0.59μMforHDAC1,HDAC2,HDAC3andHDAC11,respectively.MocetinostatshowsnoinhibitiononHDAC4,HDAC5,HDAC6,HDAC7,orHDAC8.Mocetinostat(MGCD0103)exhibitspotentandselectiveantiproliferativeactivitiesagainstabroadspectrumofhumancancercelllinesinvitro,andHDACinhibitoryactivityisrequiredfortheseeffects.Inallcelllinestested,Mocetinostat(MGCD0103)partiallyinhibitscellularHDACenzymeactivityalthoughthemaximalinhibitionofactivityvariesamongcelllinesfrom75%to85%oftotalactivity.TheIC50ofMocetinostatinintactcancercellsisindependentoftissueorigin.InA549cells,MGCD0103showsdose-dependentinhibitionofHDACactivityinwholecells.AthighconcentrationsinA549cells,Mocetinostatinhibitsamaximumof80%oftotalactivity.InHCT116cells,MocetinostatinducesasignificantS-phasedepletionandbothG1andG2-Maccumulation[1].体内研究Mocetinostat(MGCD0103)significantlyinhibitsgrowthofhumantumorxenograftsinnudemiceinadose-dependentmannerandtheantitumoractivitycorrelatedwithinductionofhistoneacetylationintumors.Thep.o.administrationofMocetinostat(MGCD0103)(2HBrsalt)significantlyreducesgrowthofimplantedadvancedA549tumorsinnudemiceinadose-dependentmannerafter13daysofdailyadministration.Mocetinostat(170mg/kgfor2HBrsalt,correspondingto120mg/kgoffreebase)significantlyblocksgrowthoftumorscomparedwithvehicletreatmentalone(P[1].PROTOCOLCellAssay[1]Cellsin96-wellplatesareincubatedwithMocetinostatatvariousconcentrationsfor72hat37°Cin5%CO2.MTTisaddedatafinalconcentrationof0.5mg/mLandincubatedwiththecellsfor4hbeforeanequalvolumeofsolubilizationbuffer[50%N,N-dimethylformamide,20%SDS(pH4.7)]isadded.Afterovernightincubation,solubilizeddyeisquantifiedbyreadingat570nmusingareferenceat630nm.Absorbancevaluesareconvertedtocellnumbersaccordingtoastandardgrowthcurveoftherelevantcellline.Theconcentrationwhichreducescellnumbersto50%relativetoDMSO-treatedcellsisdeterminedasMTTIC50[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalMice[1]Administration[1][2]FemaleCD-1nudemice,ages8to10wkareused.Tumorfragments(30mg),whichhavebeenseriallypassagedthriceinvivoinminimal,areimplanteds.c.throughasmallsurgicalincisionontheflankofthemicewhileundergeneralanesthesia.Mocetinostatisdissolvedinvehicle(PBSacidifiedwith0.1NHClorPEG400/0.2NHClsaline,40:60)anddosedp.o.assolutionsdaily.Tumorvolumesandbodyweightaremonitoredthriceweeklyforatleast2wk.Eachexperimentalgroupcontainesixtoeightanimals.Forpharmacokineticstudy,bloodiscollectedfromanimalsatvarioustimepoints,andplasmasamplesareanalyzed.Rats[2]Fortyrats(220±20g)arerandomlydividedintofourdifferentdosagesofMocetinostatgroups(Lowgroup,Mediumgroup,Highgroup,andcontrolgroupwith10ratsineachgroup).Mocetinostatisdissolvedincornoilassuspensionatthreedifferentconcentrations(20,40,and80mg/mL).ThreedifferentMocetinostatgroups(Lowgroup,Mediumgroup,andHighgroup)arerespectivelygivenMocetinostat20,40,and80mg/kgonetimebyintragastricadministrationateverymorningandlastfor7days.Controlgrouparegivensalinebysameadministrationmethod.At8daysmorning,sixprobedrugs,Bupropion,Phenacetin,Tolbutamide,Metoprolol,Testosterone,andOmeprazole,aremixedincornoilandgiventotheratsofthreeMocetinostatgroupsandcontrolgroupbyintragastricadministrationatasingledosageof10mg/kgforBupropion,Phenacetin,Metoprolol,Testosterone,andOmeprazoleand1mg/kgforTolbutamide.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CellDiscov.2022Sep14;8(1):92.•ClinCancerRes.2020Apr15;26(8):2011-2021.•ProcNatlAcadSciUSA.2019Feb19;116(8):2961-2966.•IntJOncol.2020Jun;56(6):1429-1441.•HumMolGenet.2