Birabresib-OTX-015-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBirabresibCat.No.:HY-15743CASNo.:202590-98-5Synonyms:OTX-015;MK-8628分?式:C??H??ClN?O?S分?量:491.99作?靶點(diǎn):EpigeneticReaderDomain作?通路:Epigenetics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:≥49mg/mL(99.60mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.0326mL10.1628mL20.3256mL5mM0.4065mL2.0326mL4.0651mL10mM0.2033mL1.0163mL2.0326mL請(qǐng)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(qǐng)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(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)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(qǐng)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.08mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(5.08mM);Suspendedsolution;Needultrasonic3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.08mM);Clearsolution4.請(qǐng)依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥3mg/mL(6.10mM);Clearsolution5.請(qǐng)依序添加每種溶劑：50%PEG300>>50%salineSolubility:10mg/mL(20.33mM);Clearsolution;Needultrasonicandwarmingandheatto60°CBIOLOGICALACTIVITY?物活性Birabresib(OTX-015)?種有效的BRD2/3/4抑制劑，IC50值為92-112nM。IC50&TargetIC50:92-112nM(BRD2,BRD3,BRD4)[1]體外研究Birabresib(OTX-015)(500nM)exposureinducesastrongdecreaseofBRD2,BRD4andc-MYCandincreaseofHEXIM1proteins,whileBRD3expressionisunchanged.c-MYC,BRD2,BRD3,BRD4andHEXIM1mRNAlevelsdocorrelatehoweverwithviabilityfollowingexposuretoBirabresib(OTX-015)[2].Birabresib(OTX-015)(0.1,1,5μM)treatmentinducesHIV-1full-lengthtranscriptsandviraloutgrowthinrestingCD4+Tcellsfrominfectedindividualsreceivingsuppressiveantiretroviraltherapy(ART),whileexertingminimaltoxicityandeffectsonTcellactivation.Birabresib-mediatedactivationofHIV-1involvesanincreaseinCDK9occupancyandRNAPIIC-terminaldomain(CTD)phosphorylation[3].體內(nèi)研究InMDA-MB-231murinexenografts,tumormassissignificantly(p[4].PROTOCOLCellAssay[2]FortheMTTassay,cellsareseededin24-wellplatesat1×106perwellandtreatedwithBirabresib(OTX-015)(0.01nM-10μM)for72h.Cellsaretransferredto96-wellplatesandincubatedwith0.5mg/mL3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide(MTT)inthedarkat37°Cfor4h.Cellsarethenlysedwith25%sodiumdodecylsulfate(SDS)lysisbufferandabsorbanceisreadat570nmusingaMicroplateReader.Threeindependentexperimentsarerunforeachcelllineanduntreatedcellsareusedasnegativecontrols.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMicearesubcutaneouslyinjectedintherightflankwith10×106MDA-MB-231cells.WhenaveragetumorAdministration[4]weightisappr130mg,micearerandomized(nineanimals/group)tooneofthefollowingexperimentalgroups:vehicle(forBirabresib(OTX-015),water,twicedaily,oral;forRAD001vehicle,5%Tween-80/5%polyethyleneglycol400,thriceweekly,intraperitoneal);50mg/kgBirabresib(OTX-015),twicedaily,oral;2mg/kgRAD001,thriceweekly,intraperitoneal;50mg/kgBirabresib(OTX-015)+2mg/kgRAD001,according2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEtothesingleagentdosingschedules.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Cell.2018Sep20;175(1):186-199.e19.?JExpMed.2021Aug2;218(8):e20202512.?Hepatology.2019Jun;69(6):2502-2517.?EMBOMolMed.2018May;10(5).pii:e8446.?CancerRes.2019May15;79(10):2761-2774.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].J.KayNoel,etal.AbstractC244:DevelopmentoftheBETbromodomaininhibitorOTX015.MolCancerTherNovember201312;C244.[2].Marie-MagdelaineCoudé,etal.BETinhibitorOTX015targetsBRD2andBRD4anddecreasesc-MYCinacuteleukemiacells.Oncotarget.2015Jul10;6(19):17698–17712.[3].LuP,etal.TheBETinhibitorOTX015reactivateslatentHIV-1throughP-TEFb.SciRep.2016Apr12;6:24100[4].VázquezR,etal.ThebromodomaininhibitorOTX015(MK-8628)exertsanti-tumoractivityintriple-negativebreastcancermodelsassingleagentandincombinationwithRAD001.Oncotarget.201