O6-Benzylguanine-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEO6-BenzylguanineCat.No.:HY-W002585CASNo.:19916-73-5分?式:C??H??N?O分?量:241.25作?靶點:DNA/RNASynthesis;Apoptosis作?通路:CellCycle/DNADamage;Apoptosis儲存?式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性數(shù)據(jù)體外實驗DMSO:110mg/mL(455.96mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM4.1451mL20.7254mL41.4508mL5mM0.8290mL4.1451mL8.2902mL10mM0.4145mL2.0725mL4.1451mL請根據(jù)產品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存?式和期限。體內實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案，配制前請先配制澄的儲備液，再依次添加助溶劑(為保證實驗結果的可靠性，體內實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；澄的儲備液可以根據(jù)儲存條件，適當保存；以下溶劑前的百分?指該溶劑在您配制終溶液中的體積占?)：1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.75mg/mL(11.40mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.75mg/mL(11.40mM);ClearsolutionBIOLOGICALACTIVITY1/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemE?物活性O6-Benzylguanine鳥嘌呤類似物，DNA修復酶O6烷鳥嘌呤DNA烷轉移酶(MGMT/AGT)抑制劑。O6-Benzylguanine作為AGT底物，將其芐轉移到AGT半胱氨酸殘上，從?不可逆地滅活AGT并阻?DNA修復。O6-Benzylguanine誘導腫瘤細胞凋亡，具有抗腫瘤活性。體外研究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.體內研究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?邊的抑制劑?師www.MedChemETreatRev.2006;32(4):261‐276.[2].Konduri,SanthiDetal.BlockadeofMGMTexpressionbyO6benzylguanineleadstoinhibitionofpancreaticcancergrowthandinductionofapoptosis.Clinicalcancerresearch:anofficialjournaloftheAmericanAssociationforCancerResearchvol.15,19(2009):6087-95.McePdfHeightCaution:Producthasnotbeenfullyvalida