Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemERiviciclibhydrochlorideCat.No.:HY-16559CASNo.:920113-03-7Synonyms:P276-00分?式:C??H??Cl?NO?分?量:438.3作?靶點(diǎn):CDK;Apoptosis作?通路:CellCycle/DNADamage;Apoptosis儲存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:50mg/mL(114.08mM;Needultrasonic)H2O:25mg/mL(57.04mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.2815mL11.4077mL22.8154mL5mM0.4563mL2.2815mL4.5631mL10mM0.2282mL1.1408mL2.2815mL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(sealedstorage,awayfrommoisture)。-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(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)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(shí)驗(yàn)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(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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(4.75mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.75mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.75mM);ClearsolutionBIOLOGICALACTIVITY?物活性Riviciclibhydrochloride(P276-00)有效的CDK抑制劑，抑制CDK9-cyclinT1，CDK4-cyclinD1，CDK1-cyclinB的IC50值分別為20nM，63nM，79nM[1][2]。Riviciclibhydrochloride(P276-00)對Cisplatin耐藥性細(xì)胞具有抗腫瘤活性[3]。IC50&TargetCDK9-CyclinT1cdk4-cyclinD1CDK1-CyclinBcdk2-cyclinA0.020μM(IC50)0.063μM(IC50)0.079μM(IC50)0.224μM(IC50)cdk2-cyclinEcdk6-cyclinD3CDK9-cyclinH2.500μM(IC50)0.396μM(IC50)2.900μM(IC50)體外研究Riviciclibhydrochloride(1.5-5μM;72hours)showsnodetectablecellsinG1andG2inpromyelocyticleukemiacellsandarrestofcellsinG1insynchronizedhumannon-smallcelllungcarcinoma(H-460)andhumannormallungfibroblast(WI-38)cells[3].Riviciclibhydrochloride(3-24hours;1.5μM)reducescyclinD1,Cdk4,andRblevelsinH-460cells.Rb(retinoblastoma)phosphorylationatSer780decreaseat3h[2].Riviciclibhydrochlorideshowsactivityinhumancancercelllines,suchascoloncarcinoma,osteosarcomal,cervicalcarcinoma,andbladdercarcinomacells[2].CellCycleAnalysis[3]CellLine:Promyelocyticleukemiacells(HL-60cells),non-smallcellcarcinoma(H-460)cells,humannormallungfibroblast(WI-38)cellsConcentration:1.5,5μMIncubationTime:72hoursResult:Showedapoptosisattheendof24handnodetectablecellswerepresentinG1andG2inHL-60cells.CausedanexclusiveG1arrestofsynchronouspopulationofcancerouscellsH-460cellsandnormalcellsWI-38.WesternBlotAnalysis[2]CellLine:H-460cells;MCF-7cellsConcentration:1.5μM2/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:3,6,9,12,24hoursResult:ReducedcyclinD1,Cdk4,andRblevelsinH-460cells.Rb(retinoblastoma)phosphorylationatSer780decreaseat3h.DecreasedproteinlevelsofcyclinD1andCdk4levelsstaringat6and9hinMCF-7cells,respectively,andaccompaniedbyadecreaseinphosphorylationofRbatSer780from6honward,followedbyreducedRblevelsat24h.體內(nèi)研究Riviciclibhydrochloride(administeredi.p.;35kg/mgdailyfor10days,inhumanxenograftmodewithseverecombinedimmunodeficientmice)showssignificantinhibitioninthegrowthofhumancoloncarcinomaHCT-116xenograft[3].Riviciclibhydrochloride(administeredviai.p.;50mg/kgoncedaily;30mg/kgtwicedailyfor18treatments,inhumanxenograftmodewithseverecombinedimmunodeficientmice)significantlyinhibitedgrowth[3].AnimalModel:HumanxenograftmodewithHCT-116tumormodel(severecombinedimmunodeficientmice)[3]Dosage:35mg/kgAdministration:Administeredi.p.;dailyfor10daysResult:Given35mg/kgshowedsignificantinhibitioninthegrowth.AnimalModel:HumanxenograftmodelwithH-460tumorxenograft(severecombinedimmunodeficientmice)[3]Dosage:50mg/kg;30mg/kgAdministration:Administeredi.p.;50mg/kgoncedailyfor20days;Administeredi.p.;30mg/kgtwicedailyfor18treatmentsResult:Given50mg/kgand30mg/kgtwicedailysignificantlyinhibitedgrowth.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Elife.2020Dec7;9:e61405.?IntJMolSci.2022Feb24;23(5):2493.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].RoskoskiRJr,Cyclin-dependentproteinkinaseinhibitorsincludingpalbociclibasanticancerdrugs.PharmacolRes.2016May;107:249-3/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE275.[2].JoshiKS,etal.Invitroantitumorpropertiesofanovelcyclin-dependentkinaseinhibitor,P276-00.MolCancerTher.2007Mar;6(3):918-25.[3].JoshiKS,etal.P276-00,anovelcyclin-dependentinhibitorinducesG1-G2arrest,showsantitumoractivityoncisplatin-resistantcellsandsignificantinvivoefficacyintumormode