O6-Benzylguanine-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemEO6-BenzylguanineCat.No.:HY-W002585CASNo.:19916-73-5分⼦式:C₁₂H₁₁N₅O分⼦量:241.25作⽤靶点:DNA/RNASynthesis;Apoptosis作⽤通路:CellCycle/DNADamage;Apoptosis储存⽅式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性数据体外实验DMSO:110mg/mL(455.96mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM4.1451mL20.7254mL41.4508mL5mM0.8290mL4.1451mL8.2902mL10mM0.4145mL2.0725mL4.1451mL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，并请注意储备液的保存⽅式和期限。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，配制前请先配制澄的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的⼯作液，建议您现⽤现配，当天使⽤；澄的储备液可以根据储存条件，适当保存；以下溶剂前的百分⽐指该溶剂在您配制终溶液中的体积占⽐)：1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.75mg/mL(11.40mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.75mg/mL(11.40mM);ClearsolutionBIOLOGICALACTIVITY1/3MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemE⽣物活性O6-Benzylguanine鸟嘌呤类似物，DNA修复酶O6烷鸟嘌呤DNA烷转移酶(MGMT/AGT)抑制剂。O6-Benzylguanine作为AGT底物，将其苄转移到AGT半胱氨酸残上，从⽽不可逆地灭活AGT并阻⽌DNA修复。O6-Benzylguanine诱导肿瘤细胞凋亡，具有抗肿瘤活性。体外研究TheL3.6plcellsarerelativelysensitivetoO6-Benzylguanine(24-72hours)inadose-andtime-dependentmanner.TheIC50is50μg(at48hours)[2].O6-Benzylguanine(50μg;48hours)modulatesp53downstreamtargetproteinexpression,inducesapoptosis,anddecreasescellproliferation[2].O6-Benzylguanine(50μg;48hours)significantlydecreasestheMGMTtranscriptionalactivityinL3.6pl[2].WesternBlotAnalysis[2]CellLine:L3.6plandPANC1cellsConcentration:50μgIncubationTime:48hoursResult:ExpressionsofO6methylguanineDNAmethyltransferase(MGMT),cyclinB1,cyclinB2,cyclinA,p53,andki-67weredecreased,whereasp21wasincreased.ThelevelsofcytoCandcaspase9wereincreased,whereasthelevelsofPARP1proteinweredecreased.RT-PCR[2]CellLine:L3.6plcellsConcentration:50μgIncubationTime:48hoursResult:DecreasedtheMGMTtranscriptionalactivityinL3.6pl.体内研究O6-Benzylguanine(100μg;i.p.;dailyfor35days)inhibitspancreaticcancercellgrowthandincreasespancreaticcellsensitivitytoGemcitabine(100mg/kg)[2].O6-Benzylguanineinhibitspancreaticcancercellproliferationandinducestumorcellapoptosisinvivo[2].AnimalModel:Maleathymicnudemice(NCI-nu)(bearinghumanpancreaticcancerL3.6plcells)[2]Dosage:100μgAdministration:i.p;dailyfor35daysResult:Significantlydecreasedmediantumorvolumeandweight.REFERENCES[1].RabikCA,NjokuMC,DolanME.InactivationofO6-alkylguanineDNAalkyltransferaseasameanstoenhancechemotherapy.Cancer2/3MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemETreatRev.2006;32(4):261‐276.[2].Konduri,SanthiDetal.BlockadeofMGMTexpressionbyO6benzylguanineleadstoinhibitionofpancreaticcancergrowthandinductionofapoptosis.Clinicalcancerresearch:anofficialjournaloftheAmericanAssociationforCancerResearchvol.15,19(2009):6087-95.McePdfHeightCaution:Producthasnotbeenfullyvalida