Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemE666-15Cat.No.:HY-101120CASNo.:1433286-70-4分?式:C??H??Cl?N?O?分?量:620.52作?靶點(diǎn):EpigeneticReaderDomain作?通路:Epigenetics儲存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實驗DMSO:125mg/mL(201.44mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.6116mL8.0578mL16.1155mL5mM0.3223mL1.6116mL3.2231mL10mM0.1612mL0.8058mL1.6116mL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)實驗請根據(jù)您的實驗動物和給藥?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：(為保證實驗結(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)實驗的?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%salineSolubility:≥2.08mg/mL(3.35mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(3.35mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.35mM);ClearsolutionBIOLOGICALACTIVITY?物活性666-15?種有效的選擇性CREB抑制劑，IC50為81nM。666-15抑制乳腺癌異種移植模型中的腫瘤?長。IC50&TargetIC50:81nM(CREB)[1]體外研究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,andthephosphorylationofIRE1inPE?+?siRNA?+?666-15groupandPE?+?si-CTRP3?+?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.體內(nèi)研究666-15(10mg/kg;IP;onceaweek;for11weeks)alonecanplayagoodroleininhibitingthegrowthofbreastcancer,andthecombinationwithRP-56976(DOC)showsabettereffect[2].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalModel:1-month-oldfemalenudemicewithMDA-MB-231orT47Dcells[2]Dosage:10mg/kgAdministration:IP;onceaweek;for11weeksResult:Playedagoodroleininhibitingthegrowthofbreastcancer.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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