Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESIRT6activator12qCat.No.:HY-148712CASNo.:2601734-99-8分?式:C??H??N?O?分?量:454.52作?靶點(diǎn):Apoptosis;Sirtuin作?通路:Apoptosis;CellCycle/DNADamage;Epigenetics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:25mg/mL(55.00mM;ultrasonicandwarmingandheatto70°C)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.2001mL11.0006mL22.0012mL5mM0.4400mL2.2001mL4.4002mL10mM0.2200mL1.1001mL2.2001mL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；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。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%DMSO>>90%cornoilSolubility:≥1.25mg/mL(2.75mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性SIRT6activator12q有效的、選擇性的和具有?服活性的SIRT6激活劑，對(duì)SIRT1、SIRT2、SIRT3、SIRT5、SIRT6的IC50值分別為171.20、>200、>200、>200、0.58μM。SIRT6activator12q抑制細(xì)胞?長(zhǎng)和遷移。SIRT6activator12q誘導(dǎo)細(xì)胞凋亡(Apoptosis)和細(xì)胞周期停滯在G2期。SIRT6activator12q顯?出抗癌活性[1]。IC50&TargetSIRT1SIRT2SIRT3SIRT5171.2μM(IC50)>200μM(IC50)>200μM(IC50)>200μM(IC50)SIRT60.58μM(IC50)體外研究SIRT6activator12q(compound12q)(2.5,5,10μM;14,18days)inhibitsthecolonyformationofPANC-1,BXPC-3,MIAPaCa-2,andAsPC-1cellsinadose-dependentmanner[1].SIRT6activator12q(10,25,50μM;48h)inducesapoptosisandcellcyclearrestatG2phaseinadose-dependentmanner[1].SIRT6activator12q(12.5,25,50μM;48h)decreasestheproteinexpressionofH3K9ac,H3K18ac,andH3K56acinPANC-1andBXPC-3cellsinadose-dependentmanner[1].CellViabilityAssay[1]CellLine:PANC-1,BXPC-3,MIAPaCa-2,andAsPC-1cellsConcentration:0-100μMIncubationTime:72hResult:ShowedantiproliferativeactivitywithIC50sof4.43,8.27,7.10,9.66μMforPANC-1,BXPC-3,MIAPaCa-2,andAsPC-1cells,respectively.CellCycleAnalysis[1]CellLine:PANC-1,BXPC-3cellsConcentration:10,25,50μMIncubationTime:48hResult:InducedcellcyclearrestatG2phaseinadose-dependentmanner.ApoptosisAnalysis[1]CellLine:PANC-1,BXPC-3cellsConcentration:10,25,50μM2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:48hResult:InducedapoptosisbyincreasedAnnexinV+populationsinaconcentration-dependentmanner.WesternBlotAnalysis[1]CellLine:PANC-1,BXPC-3cellsConcentration:12.5,25,50μMIncubationTime:72hResult:DecreasedtheproteinlevelsofH3K9ac,H3K18ac,andH3K56acinPANC-1andBXPC-3cellsinadose-dependentmanner.體內(nèi)研究SIRT6activator12q(100,150mg/kg;p.o.;dailyfor30days)inhibitesthetumergrowthinadose-dependentmannerinmouse[1].PharmacokineticParametersofSIRT6activator12qinMaleSprague-Dawleyrats[1].PKparameter10mg/kgp.o.2mg/kgi.v.CL(L/h/kg)0.6±0.08Vss(L/kg)1112.8±322.84T1/2(h)7.52±1.449.06±0.21Tmax(h)2.00±0.000.08±0.00Cmax(ng/mL)98.45±3.625123.70±905.5AUC(0-t)(h·ng/mL)704.67±80.473326.13±476.4AUC(0-∞)(h·ng/mL)755.57±80.743381.49±468.48F(%)4.24±0.48MaleSprague-Dawleyrats,2mg/kgiv;10mg/kgpo[1]AnimalModel:BALB/cfemalenudemice(humanpancreatictumorxenograftmodelofPANC-1)[1]Dosage:100,150mg/kgAdministration:P.o.;dailyfor30daysResult:Inhibitedtumergrowthinadose-dependentmanner,andatumorinhibitionrateof90.25%atadoseof150mg/kg.REFERENCES[1].ChenX,etal.DiscoveryofPotentSmall-MoleculeSIRT6Activators:Structure-ActivityRelationshipandAnti-PancreaticDuctalAdenocarcinomaActivity.JMedChem.2020Sep24;63(18):10474-10495.McePdfHeightCaution