NHWD-870-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemENHWD-870Cat.No.:HY-134463CASNo.:2115742-03-3分?式:C??H??N?O分?量:491.59作?靶點(diǎn):EpigeneticReaderDomain;Apoptosis作?通路:Epigenetics;Apoptosis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:125mg/mL(254.28mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.0342mL10.1711mL20.3422mL5mM0.4068mL2.0342mL4.0684mL10mM0.2034mL1.0171mL2.0342mL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(chǔ)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(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(4.23mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.23mM);ClearsolutionBIOLOGICALACTIVITY?物活性NHWD-870?種?效、?服活性和選擇性的BETfamilybromodomain抑制劑，僅與BRD2、BRD3、BRD4(IC50=2.7nM)和BRDT結(jié)合。NHWD-870具有較強(qiáng)的抑癌作?，并能抑制癌細(xì)胞與巨噬細(xì)胞的相互作?。體外研究NHWD-870(0.01-10000nM)inhibitsmelanomacells(A375)withanIC50of2.46nM[1].NHWD-870(0-10000nM;5dys)suppressedcellgrowth[1].NHWD-870(0-50nM;24?hours)inhibitsBRD4phosphorylationandc-MYCexpression[1].NHWD-870exhibitsmildinhibitionofhERGchannel(IC50?=?5.4?μM)[1].NHWD-870showsrobustactivitiesinducingapoptosisandsuppressingcellproliferation[1].CellViabilityAssay[1]CellLine:H526,A2780,ES-2,andMDA-MB231cellsConcentration:0-10000nMIncubationTime:5daysResult:Showedstronginhibitoryactivitiesagainstthesecellsin5-dayassays.WesternBlotAnalysis[1]CellLine:H526,A2780,ES-2,andMDA-MB231cellsConcentration:0-50nMIncubationTime:24?hoursResult:LedtothedepletionofphosphorylatedBRD4andc-MYCat10nM.體內(nèi)研究NHWD-870(0.75-3mg/kg;p.o.)hasstronganti-tumoractivitiesinmousemodels[1].NHWD-870reducesthenumberoftumorassociatedmacrophages(TAMs)insubcutaneouslyimplantedH526andA2780tumors.NHWD-870downregulatedCSF1expressionintumorcellstoinhibitTAMproliferation[1].NHWD-870manifestsdiversemechanismsofactionindifferentcancersettings.Theseinclude:1)inhibitionoftumorcellgrowthbydownregulatingthePDGFRβ,MEK1/2andSTAT1/MYCsignalingintumorcells;2)inhibitionoftumorangiogenesisbydecreasingPDGFproductionintumorcellsandthePDGFRβandMEK1/2signalinginendothelialcells.NHWD-870haspotenttumorsuppressiveefficaciesinxenograftmousemodelsofsmallcelllungcancer,triplenegativebreastcancerandovariancancer[2].AnimalModel:4-6weeksoldfemaleBALB/cnudemice/6-8weeksoldfemaleC57BL/6micewereused2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEforB16F10experiments(bearingNCI-H526,A2780,A375,B16F10,andTMD-8cells)[1]Dosage:0.75-3mg/kgAdministration:P.o.;TMD8andB16F10melanomamodelwithoncedailyfor11-21days;A375melanomaandPDXofmelanomawithoncedaily(5dayson,2daysoff)for21days.Result:Stronglysuppressedthegrowthofestablishedlungtumor,ovariantumor,lymphoma,andmelanomainvivo.REFERENCES[1].YinM,etal.PotentBRD4inhibitorsuppressescancercell-macrophageinteraction.NatCommun.2020;11(1):1833.Published2020Apr14.[2].NenghuiWang,etal.Abstract1382:AnovelBETfamilybromodomaininhibitorNHWD-870representsapromisingtherapeuticagentforabroadspectrumofcancers.MolecularandCellularBiology,Genetics.McePdfHeightCaution:Produ