Seliciclib-Roscovitine-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESeliciclibCat.No.:HY-30237CASNo.:186692-46-6Synonyms:Roscovitine;CYC202;R-roscovitine分⼦式:C₁₉H₂₆N₆O分⼦量:354.45作⽤靶点:CDK作⽤通路:CellCycle/DNADamage储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥100mg/mL(282.13mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.8213mL14.1064mL28.2127mL5mM0.5643mL2.8213mL5.6425mL10mM0.2821mL1.4106mL2.8213mL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)1/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(7.05mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.05mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.05mM);Clearsolution4.请依序添加每种溶剂：10%DMSO>>90%salineSolubility:5mg/mL(14.11mM);Suspendedsolution;Needultrasonic5.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(7.05mM);Clearsolution6.请依序添加每种溶剂：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.05mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Seliciclib(Roscovitine)⼀种有效的，具有⼝服活性的，选择性的CDKs抑制剂，抑制CDK5，Cdc2和CDK2的IC50分别为0.2μM，0.65μM，0.7μM。IC50&Targetcdc2/cyclinBcdk2/cyclinACdk2/cyclinE2CDK5/p350.65μM(IC50)0.7μM(IC50)0.7μM(IC50)0.16μM(IC50)GST-erk1erk1erk2IRtyrosinekinase30μM(IC50)34μM(IC50)14μM(IC50)70μM(IC50)体外研究Seliciclib(Roscovitine)displayshighefficiencyandhighselectivitytowardssomecyclin-dependentkinases.ThekinasespecificityofSeliciclibisinvestigatedwith25highlypurifiedkinases(includingproteinkinaseA,GandCisoforms,myosinlight-chainkinase,caseinkinase2,IRtyrosinekinase,c-src,v-abl).MostkinasesarenotsignificantlyinhibitedbySeliciclib(Roscovitine).Cdc2,Cdk2,andCdk5onlyaresubstantiallyinhibited(IC50valuesof0.65,0.7,and0.2μM,respectively).Cdk4kandCdk6areverypoorlyinhibitedbySeliciclib(Roscovitine)(IC50>100μM).Extracellularregulatedkinaseserk1anderk2areinhibitedwithanIC50of34μMand14μM,respectively.Seliciclib(Roscovitine)inhibitstheproliferationofmammaliancelllineswithanaverageIC50of16μM[1].SeliciclibdecreasesthelevelofCDK5andp35withupregulationofE-cadherin,butdownregulationofVimentinandCollagenIV.Moreover,Seliciclib(Roscovitine)inhibitstheabilityofhighglucoseculturedNRK52Ecellstomigrateandinvade[2].体内研究Comparewithnormalcontrols,Seliciclib(Roscovitine)downregulatesphosphorylatedERK1/2andPPARγwithconcomitantincreaseinE-cadherin,butdecreaseinVimentinandCollagenIV.Correspondingly,Seliciclibdecreasesrenaltubulointerstitialfibrosisofdiabeticrats.Seliciclib(Roscovitine)iseffectiveindecreasingtubulointerstitialfibrosisviatheERK1/2/PPARγpathwayindiabeticrats[2].Seliciclib(Roscovitine)(16.5mg/kg)significantlyreducestherateoftumorgrowthandincreasessurvivaloftreatedmice.Strikingly,Seliciclib(Roscovitine)treatmentleadstocompletetumordisappearanceinonemouse(25%);moreover,notumorregrowthinthismouseisfound5monthsaftercompletionofthetreatment.MouseweightsdonotdiffersignificantlybetweenmicetreatedwithSeliciclibandcontrolmice,and2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEbehavioraldifferencesbetweenthetwogroupsarealsonegligible.TheseresultssuggestthatSeliciclibcanbeusedeffectivelyasaselectivetumorgrowthinhibitorinHPV+headandneckcancer[3].PROTOCOLCellAssay[2]Ratkidneytubularepithelialcells(NRK52E)areused.CDK5inhibitorSeliciclib(Roscovitine)(Ros.;10μM)andactivatorp35(15μM),PPARγagonistBRL49653(Rosi.;50nM),andERK1/2inhibitorU0126(50nM)areusedtotreatNRK52Ecells.Cellsineachgrouparetreatedfor72hoursandthenharvestedforfurtheranalyses[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalRats[2]Administration[2][3]MaleSpragueDawleyrats(6-8weeksofage)aregivenintraperitoneallyasingleinjectionofeitherStreptozotocin(65mg/kg)dilutedin0.1McitratebufferpH4.5(diabetic)orcitratebuffer(non-diabetic).Plasmaglucoseconcentrationsaredeterminedusingtheglucoseoxidasemethodonaglucoseanalyzerthreedaysaftertheinjection.Ratswithaglucoselevelover16.7mMareconsidereddiabeticandthusincludedinthestudy.Plasmaglucoselevelismeasuredonceeveryweek.ToinvestigatetheeffectofCDK5inhibitiononrenaltubulointerstitialfibrosis,Seliciclib(25mg/kg)isinjectedperitoneallytodiabeticratseverydaytillsacrifice.DMSOisincludedascontrols.Mice[3]ExponentiallygrowingUMSCC47cellsareinjectedsubcutaneouslyintothesacralareaoffemaleNUDEmice.Eachmouseisinoculatedwith2×105cellsin50%matrigeland50%PBSatavolumeof100μL.Aftertumorsreachameasurablesize,themicearegiven16.5mg/kgdosesofintraperitonealSelicicliborvehicleinjections.Bodyweight,tumorgrowth,andgeneralbehavioraremonitored.Tumorvolumesaremeasuredevery3days.Micearesacrificedwhenthetumorexceededasizeof0.5cm3.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•Nature.2020Sep;585(7824):293-297.•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•CellDeathDiffer.2021Jan;28(1):337-348.•CellSyst.2018Apr25;6(4):424-443.e7.•RedoxBiol.22July2022,102418.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MeijerL,etal.Biochemicalandcellulareffec