Mocetinostat-MGCD0103-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMocetinostatCat.No.:HY-12164CASNo.:726169-73-9Synonyms:MGCD0103分?式:C??H??N?O分?量:396.44作?靶點(diǎn):HDAC;Autophagy;Apoptosis作?通路:CellCycle/DNADamage;Epigenetics;Autophagy;Apoptosis儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:50mg/mL(126.12mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.5224mL12.6122mL25.2245mL5mM0.5045mL2.5224mL5.0449mL10mM0.2522mL1.2612mL2.5224mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(5.25mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(5.25mM);ClearsolutionBIOLOGICALACTIVITY?物活性Mocetinostat(MGCD0103)?種有效，可?服和同種型選擇性的HDAC(ClassI/IV)抑制劑，抑制HDAC1，HDAC2，HDAC3和HDAC11的IC50分別為0.15，0.29，1.66和0.59μM。Mocetinostat對(duì)HDAC4，HDAC5，HDAC6，HDAC7或HDAC8沒(méi)有抑制作?。IC50&TargetHDAC1HDAC2HDAC11HDAC30.15μM(IC50)0.29μM(IC50)0.59μM(IC50)1.66μM(IC50)體外研究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].體內(nèi)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?邊的抑制劑?師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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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