666-15-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemE666-15Cat.No.:HY-101120CASNo.:1433286-70-4分⼦式:C₃₃H₃₁Cl₂N₃O₅分⼦量:620.52作⽤靶点:EpigeneticReaderDomain作⽤通路:Epigenetics储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:125mg/mL(201.44mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.6116mL8.0578mL16.1155mL5mM0.3223mL1.6116mL3.2231mL10mM0.1612mL0.8058mL1.6116mL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；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。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。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(3.35mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(3.35mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.35mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性666-15⼀种有效的选择性CREB抑制剂，IC50为81nM。666-15抑制乳腺癌异种移植模型中的肿瘤⽣长。IC50&TargetIC50:81nM(CREB)[1]体外研究666-15(73nM;for12hours)significantlyblockstheeffectscausedbyMSNoverexpression,includingcellproliferation,invasion,softagarcolonyformationability,andtheexpressionofCREBdownstreamgenes.666-15inhibitsMSNoverexpression-inducedCREBphosphorylation[2].666-15(1μM;pretreated2hour)effectivelyinhibitsPE-inducedCREBphosphorylation.666-15significantlydecreasestheproteinexpressionofANPandβ-MHCandinhibitstheactivationofERstress,includingtheexpressionofGRP78,CHOP,ATF6,andthephosphorylationofIRE1inPEꢀ+ꢀsiRNAꢀ+ꢀ666-15groupandPEꢀ+ꢀsi-CTRP3ꢀ+ꢀ666-15group[3].666-15potentlyinhibitscancercellgrowth.InMDA-MB-231andMDA-MB-468cells,theGI50for666-15is73and46nM,respectively.InA549andMCF-7cells,itexhibitsrobustactivityaswellwithGI50of0.47and0.31μM.666-15isalsofoundtobearatherweakinhibitorofCREB-CBPinteractionwithIC50of18.27μM.666-15inhibitsCREB’stranscriptionactivityinlivingcellsindependentofdirectCREBorCBPbindinginteraction.666-15isverypotentininhibitingCREB’stranscriptionactivity.666-15alsoinhibitsendogenousCREBtargetgeneexpression,thetranscriptlevelofnuclearreceptorrelated1protein(Nurr1/NR4A2)[1].CellProliferationAssay[2]CellLine:CTRLorMSN-overexpressingMDA-MB-231cellsConcentration:73nMIncubationTime:For12hoursResult:SignificantlyblockedthecellproliferationcausedbyMSNoverexpression.WesternBlotAnalysis[3]CellLine:NRCMsConcentration:1μMIncubationTime:2hour(pretreated)Result:EffectivelyinhibitedPE-inducedCREBphosphorylation.体内研究666-15(10mg/kg;IP;onceaweek;for11weeks)alonecanplayagoodroleininhibitingthegrowthofbreastcancer,andthecombinationwithRP-56976(DOC)showsabettereffect[2].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalModel:1-month-oldfemalenudemicewithMDA-MB-231orT47Dcells[2]Dosage:10mg/kgAdministration:IP;onceaweek;for11weeksResult:Playedagoodroleininhibitingthegrowthofbreastcancer.户使⽤本产品发表的科研⽂献•NatCommun.2022Nov28;13(1):7323.•NatCommun.2022Nov4;13(1):6648.•SciAdv.2020Feb19;6(8):eaaw9960.•ActaPharmSinB.13October2022.•JExpClinCancerRes.2021Oct27;40(1):340.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].XieF,etal.IdentificationofaPotentInhibitorofCREB-MediatedGeneTranscriptionwithEfficaciousinVivoAnticancerActivity.JMedChem.2015Jun25;58(12):5075-87.[2].ZhangB,etal.C1q-TNF-relatedprotein-3attenuatespressureoverload-inducedcardiachypertrophybysuppressingthep38/CREBpathwayandp38-inducedERstress.CellDeathDis.2019Jul8;10(7):520.[3].QinY,etal.InterferingMSN-NONOcomplex-activatedCREBsignalingservesasatherapeuticstrategyfortriple-negativebreastcancer.SciAdv.2020Feb19;6(8):ea