JIB-04-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEJIB-04Cat.No.:HY-13953CASNo.:199596-05-9分?式:C??H??ClN?分?量:308.76作?靶點(diǎn):HistoneDemethylase;Apoptosis作?通路:Epigenetics;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:30mg/mL(97.16mM;Needultrasonic)掃描?維碼，Ethanol:2mg/mL(6.48mM;Needultrasonic)運(yùn)?溶解?案計(jì)算器獲得適合您實(shí)驗(yàn)體系的溶解?案MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.2388mL16.1938mL32.3876mL5mM0.6478mL3.2388mL6.4775mL10mM0.3239mL1.6194mL3.2388mL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，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。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：0.5%CMC-Na/salinewater2.Solubility:10mg/mL(32.39mM);Suspendedsolution;Needultrasonic請(qǐng)依序添加每種溶劑：10%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.08mg/mL(6.74mM);Clearsolution此?案可獲得≥2.08mg/mL(6.74mM，飽和度未知)的澄溶液。1/3www.MedChemEwww.MedChemE以1mL?作液為例，取100μL20.8mg/mL的澄DMSO儲(chǔ)備液加到400μLPEG300中，混合均勻；向上述體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。BIOLOGICALACTIVITY?物活性JIB-04Jumonji組蛋?去甲酶(Jumonjihistonedemethylase)?譜抑制劑，能抑制JARID1A，JMJD2E，JMJD3，JMJD2A，JMJD2B，JMJD2C和JMJD2D的活性，其IC50值分別為230，340，855，445，435，1100和290nM。IC50&TargetIC50:230nM(JARID1A),445nM(JMJD2A),435nM(JMJD2B),1100nM(JMJD2C),290nM(JMJD2D),340nM(JMJD2E),855nM(JMJD3)[1]體外研究JIB-04isconsistentlyselectiveforcancervs.normalcells,demonstratedbythehighersensitivityoflungandprostatecancerlines(withIC50aslowas10nM)comparedtoHBECsandPrSCs/PrECs.JIB-04inhibitscellularJumonjidemethylaseactivity,andJumonjilevelsaffectJIB-04actionincells[1].JIB-04significantlyinhibitstheproliferationofGBcelllinesandstem-enrichedcultures.JIB-04exertsitsmaximalinhibitoryactivityagainstKDM5A,andmodulatestheexpressionofgenesinvolvedinthecontrolofcancercellgrowthandleadstohypermethylationofH3K4.Furthermore,JIB-04(2500nM)activatestheautophagyandapoptoticpathwaysandinactivatesPI3K.JIB-04alsocooperateswithTMZinkillingGBcells[2].體內(nèi)研究JIB-04resultsinasignificantreductionincancer-induceddeathratesinmice,prolongingsurvival[1].JIB-04(60,40and20mg/kg,i.p.)reachesbioactiveconcentrationinthebrainofthemice.TheorthotopicGBxenograftmodelshowsatrendtowardlongersurvivalinJIB-04-treatedmicewithanHazardRatioof0.5[2].PROTOCOLCellAssay[1]Forcellviabilityassays,cellsareplatedat1500-3000cells/wellin96wellplatesandtreatedthenextdaywithincreasingdosesofcompoundover4daysandtheirviabilityassessedbystandardMTSassaysusingPromega’sCellTiterorCellTiter-Gloreagents.Absorbanceat490nmand650nmorluminescenceismeasuredbyaSpectraMaxoraFlouroStarOmegaplatereader.Dataarenormalizedtotheuntreatedcontrols(100%viability).Eachcelllineistestedin2-5independentassays,eachcontaining4-8replicates.IC50valuesarecalculatedusingDIVISA,ahigh-throughputsoftware,developedinhouse,forstoringandanalyzingdrugsensitivityassays.Dose-responsecurvesareplottedusinganon-linearregressionmodelandIC50saredeterminedfromthefittedcurves.TheaverageIC50derivedfrom2-5independentassays,eachcontaining4-8replicatesisreported.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalForxenografts,4-6weekoldfemalenudemicearehousedunderstandardconditionsinacleanfacilityatAdministration[1]UTSW.TwomillionH358cellsorfivemillionA549cellsareinjectedsubcutaneouslyandallowedtogrowfor2-3weekswithmonitoring.Whentumorsreachappr200mm3,therapyisstartedinweightandtumorvolumematchedpairs(n=7foreachtreatmentgroupforeachcellline).Drugorvehicleisadministeredbyinter-peritonealinjectionin10%DMSO90%sesameoil2to3timesweeklyfor5weeksat110mg/kgtoallmiceharboringH358xenograftsor3timesperweekbygavagein12.5%CremophorEL,12.5%DMSOasan2/3www.MedChemEwww.MedChemEaqueoussuspensionat55mg/kgtomiceharboringA549xenografts.Tumorvolumesaremonitoredtwiceweeklybycalipermeasurements.Animalsareweighedandobservedduringthefiveweeksoftreatment.Attheendpoint,miceareeuthanizedbyCO2asphyxiationandcervicaldislocation,andblood,tumorsandmajororganscollectedandweighed.Paired,unequalvariance,one-tailedt-testsareperformedacrosstreatmentgroupsusingExcelsoftware.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?CancerCell.2019Apr15;35(4):677-691.e10.?ProcNatlAcadSciUSA.2019Feb19;116(8):2961-2966.?ACSMedChemLett.2015Jun22;6(8):948-52.?JReceptSignalTransductRes.2020Aug;40(4):339-347.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WangL,etal.AsmallmoleculemodulatesJumonjihistonedemethylaseactivityandselectivelyinhibitscancergrowth.NatCommun,2013.4:p.2035.[2].BanelliB,etal.Smallmoleculestargetinghistonedemethylasegenes(KDMs)inhibitgrowthoftemozolomide-resistantglioblastomacells.Oncotarget.2017Apr4.Mce