Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESeliciclibCat.No.:HY-30237CASNo.:186692-46-6Synonyms:Roscovitine;CYC202;R-roscovitine分?式:C??H??N?O分?量:354.45作?靶點:CDK作?通路:CellCycle/DNADamage儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥100mg/mL(282.13mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.8213mL14.1064mL28.2127mL5mM0.5643mL2.8213mL5.6425mL10mM0.2821mL1.4106mL2.8213mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?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)1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(7.05mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.05mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.05mM);Clearsolution4.請依序添加每種溶劑：10%DMSO>>90%salineSolubility:5mg/mL(14.11mM);Suspendedsolution;Needultrasonic5.請依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(7.05mM);Clearsolution6.請依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.05mM);ClearsolutionBIOLOGICALACTIVITY?物活性Seliciclib(Roscovitine)?種有效的，具有?服活性的，選擇性的CDKs抑制劑，抑制CDK5，Cdc2和CDK2的IC50分別為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)體外研究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].體內(nèi)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?邊的抑制劑?師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.戶使?本產(chǎn)品發(fā)表的科研?獻?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