BRD9876-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBRD9876Cat.No.:HY-110208CASNo.:32703-82-5分⼦式:C₁₆H₁₄N₂分⼦量:234.3作⽤靶点:Kinesin;Microtubule/Tubulin作⽤通路:CellCycle/DNADamage;Cytoskeleton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:50mg/mL(213.40mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM4.2680mL21.3402mL42.6803mL5mM0.8536mL4.2680mL8.5361mL10mM0.4268mL2.1340mL4.2680mL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>>90%cornoilSolubility:≥2.5mg/mL(10.67mM);Clearsolution1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性BRD9876⼀种“rigor”抑制剂，可将驱动蛋⽩5(Eg5)锁定在增强微管(MTs)结合的状态，从⽽导致MT的捆绑和稳定。BRD9876与酪氨酸104残相互作⽤，该残α4-α6变构结合⼝袋的⼀部分。BRD9876特异性靶向微管结合的Eg5，选择性抑制CD34细胞的⾻髓瘤。BRD9876具有⽤于多发性⾻髓瘤(MM)研究的潜⼒。体外研究BRD9876(10μM;24hours)revealesrapidarrestofcellsattheG2/Mphasestartingasearlyas2hoftreatmentinMM1Scells[1].BRD9876exhibitsapproximately3-foldselectivityforMM1Smyelomacells(IC50=3.1μM)overCD34+derivedhematopoieticcells(IC50=9.1μM)[1].BRD9876(0.1,1,10,100uM)isabletoovercome,inMM1Scells,stromalresistanceofbonemarrowstromalcells(BMSCs)fromMMbonemarrowaspiratesbutonlyminimaleffectsareobservedwithBRD9876againstprimaryMMcells[1].BRD9876iscompletelyineffectiveatinhibitingthebasalATPaseactivityofEg5,incontrasttoloopL5-bindingmonastrolorα4/α6-bindingBI8whichshowsgreateractivityagainstbasalEg5ATPaseactivity[1].CellCycleAnalysis[1]CellLine:MM1ScellsandCD34hematopoieticcellsConcentration:10μMIncubationTime:24hoursResult:RevealedrapidarrestofcellsattheG2/Mphasestartingasearlyas2hoftreatmentinMM1Scells.ShowedmarkedlylessG2/MarrestinCD34hematopoieticcells.REFERENCES[1].ShrikantaChattopadhyay,etal.Niche-BasedScreeninginMultipleMyelomaIdentifiesaKinesin-5InhibitorwithImprovedSelectivityoverHematopoieticProgenitors.CellRep.2015Feb10;10(5):755-770.[2].Geng-YuanChen,etal.Eg5InhibitorsHaveContrastingEffectsonMicrotubuleStabilityandMetaphaseSpindleIntegrity.ACSChemBiol.2017Apr21;12(4):1038-1046.[3].Chieh-TingFang,etal.HSP70regulatesEg5distributionwithinthemitoticspindleandmodulatesthecytotoxicityofEg5inhibitors.CellDeathDis.2020Sep1;11(8):715.[4].AnkeMaes,etal.Thetherapeuticpotentialofcellcycletargetinginmultiplemyeloma.Oncotarget.2017Jun28;8(52):90501-90520.McePdfHeightCaution:Producthasnotbeenfullyvalidatedfor