Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemECytarabineCat.No.:HY-13605CASNo.:147-94-4分?式:C?H??N?O?分?量:243.22作?靶點(diǎn):DNA/RNASynthesis;NucleosideAntimetabolite/Analog;HSV;Autophagy;EndogenousMetabolite;Apoptosis作?通路:CellCycle/DNADamage;Anti-infection;Autophagy;MetabolicEnzyme/Protease;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)H2O:48mg/mL(197.35mM;Needultrasonic)掃描?維碼，DMSO:17.3mg/mL(71.13mM;Needultrasonicand運(yùn)?溶解?案計(jì)算器warming)獲得適合您實(shí)驗(yàn)體系的溶解?案MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM4.1115mL20.5575mL41.1150mL5mM0.8223mL4.1115mL8.2230mL10mM0.4112mL2.0558mL4.1115mL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?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶1.請(qǐng)依序添加每種溶劑：10%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.08mg/mL(8.55mM);Clearsolution此?案可獲得≥2.08mg/mL(8.55mM，飽和度未知)的澄溶液。1/4www.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2.體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。請(qǐng)依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(8.55mM);Clearsolution此?案可獲得≥2.08mg/mL(8.55mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL20.8mg/mL的澄DMSO儲(chǔ)備液加到900μL20%的SBE-β-CD?理鹽??溶3.液中，混合均勻。請(qǐng)依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥2.08mg/mL(8.55mM);Clearsolution此?案可獲得≥2.08mg/mL(8.55mM，飽和度未知)的澄溶液，此?案不適?于實(shí)驗(yàn)周期在半個(gè)?以上的實(shí)驗(yàn)。4.以1mL?作液為例，取100μL20.8mg/mL的澄請(qǐng)依序添加每種溶劑：PBSDMSO儲(chǔ)備液加到900μL??油中，混合均勻。Solubility:130mg/mL(534.50mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Cytarabine?種核苷類似物，可引起S期細(xì)胞周期停滯并抑制DNA聚合酶。Cytarabine抑制DNA合成的IC50為16nM。Cytarabine對(duì)HSV具有抗病毒作?。IC50&TargetHumanEndogenousHSV-1Metabolite體外研究Cytarabineisphosphorylatedintoatriphosphateform(Ara-CTP)involvingdeoxycytidinekinase(dCK),whichcompeteswithdCTPforincorporationintoDNA,andthenblocksDNAsynthesisbyinhibitingthefunctionofDNAandRNApolymerases.Cytarabinedisplaysahighergrowthinhibitoryactivitytowardswild-typeCCRF-CEMcellscomparedtootheracutemyelogenousleukemia(AML)cellswithIC50of16nM[1].Cytarabineapparentlyinducesapoptosisofratsympatheticneuronsat10μM,ofwhich100μMshowsthehighesttoxicityandkillsover80%oftheneuronsby84hours,involvingthereleaseofmitochondrialcytochrome-candtheactivationofcaspase-3,andthetoxicitycanbeattenuatedbyp53knockdownanddelayedbybaxdeletion[2].體內(nèi)研究Cytarabine(250mg/kg)alsocausesplacentalgrowthretardationandincreasesplacentaltrophoblasticcellsapoptosisintheplacentallabyrinthzoneofthepregnantSlc:Wistarrats,whichincreasesfrom3hourafterthetreatmentandpeaksat6hourbeforereturningtocontrollevelsat48hour,withremarkablyenhancedp53protein,p53trancriptionaltargetgenessuchasp21,cyclinG1andfasandcaspase-3activity[3].Cytarabineishighlyeffectiveagainstacuteleukaemias,whichcausestheCytarabineteristicG1/Sblockageandsynchronization,andincreasesthesurvivaltimeforleukaemicBrownNorwayratsinaweakdose-relatedfashionindicatingthattheuseofhigherdosagesofCytarabinedoesnotcontributetoitsantileukaemiceffectivenessinman[4].PROTOCOLAnimalPregnantratsareinjectedintraperitoneally(i.p.)with250mg/kgofCytarabineonDay13ofgestation2/4www.MedChemEwww.MedChemEAdministration[3](GD13).Undertheconditionsofthisexperiment,congenitalanomaliesandgrowthretardationaredetectedatahighrateinperinatalfetuses,althoughtheincidenceoffetaldeathisnotmarkedlyincreased.At1,3,6,9,12,24,and48hafterthetreatment,sixdamseacharekilledbyheartpunctureunderetheranesthesia,andtheplacentasarecollected.Ascontrols,sixpregnantratsareinjectedi.p.withanequivalentvolumeofPBSonGD13andkilledatthesametimepointasCytarabine-treatedgroups.Ofthesixdamsobtainedateachtimepoint,threeareusedforhistopathologicalanalysesandthreeforreversetranscription-polymerasechainreaction(RT-PCR)analysis.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Cell.2018Sep20;175(1):171-185.e25.?Leukemia.2021Mar29.?ClinChem.2019Dec;65(12):1522-1531.?CellDeathDis.2021Jan5;12(1):20.?ActaPharmacolSin.2021Jan;42(1):108-114.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].Tobias,S.C.andR.F.Borch,Synthesisandbiologicalevaluationofacytarabinephosphoramidateprodrug.MolPharm,2004.1(2):p.112-6.[2].Besirli,C.G.,etal.CytosinearabinosiderapidlyactivatesBax-dependentapoptosisandadelayedBax-independentdeathpathwayinsympatheticneurons.CellDeathDiffer,2003.10(9):p.1045-58.[3].Yamauchi,H.,etal.,Involvementofp53in1-beta-D-arabinofuranosylcytosine-inducedtrophoblasticcellapoptosisandimpairedproliferationinratplacenta.BiolReprod,2004.70(6):p.1762-7.[4].Richel,D.J.,etal.,Comparisonoftheantileukaemicactivityof5aza-2-deoxycytidineandarabinofuranosyl-cytosineinratswithmyelocyticleukaemia.BrJCancer,1988.58(6):p.730-3.[5].ShepshelovichD,etal.Pharmacodynamicsofcytarabineinducedleucopenia:aretrospectivecohortstudy.BrJClinPharmacol.2015Apr;79(4):685-91.[6].RenisHE.Antiviralactivityofcytarabineinherpesvir