BSJ-4-116-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBSJ-4-116Cat.No.:HY-139039CASNo.:2519823-34-6分?式:C??H??ClN?O?S分?量:837.38作?靶點(diǎn):PROTACs;CDK作?通路:PROTAC;CellCycle/DNADamage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:250mg/mL(298.55mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.1942mL5.9710mL11.9420mL5mM0.2388mL1.1942mL2.3884mL10mM0.1194mL0.5971mL1.1942mL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(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(2.48mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(2.48mM);ClearsolutionBIOLOGICALACTIVITY?物活性BSJ-4-116由Cereblon配體和CDK配體相連的PROTAC。BSJ-4-116?種?效且選擇性的CDK12降解劑，IC50為6nM。BSJ-4-116通過提前終?轉(zhuǎn)錄來下調(diào)DDR因，主單獨(dú)或與聚(ADP-核糖)聚合酶抑制劑Olaparib(HY-10162)聯(lián)合使?時(shí)表現(xiàn)出有效的抗增殖作?。IC50&TargetCDK12Cereblon6nM(IC50)體外研究BSJ-4-116(10-10000nM;72hours)exhibitspotentantiproliferativeeffectsinKellyCDK12C1039F[1].BSJ-4-116(50?nM;6-24?hours)decreasesthelevelofCDK12protein,regardlessofthemutationalstatusofthecellline[1].BSJ-4-116inhibitsthegrowthofT-ALLcells(JurkatandMOLT-4cells)andsensitizesthemtoPARPinhibition[1].BSJ-4-116regulatesDDRgenesviapoly(adenylation).BSJ-4-116overcomesCDK12C1039Fmutation.BSJ-4-116representsthefirstexampleofresistancetoabivalentdegradermoleculethatisaconsequenceofanacquiredpointmutationinthetargetprotein[1].CellProliferationAssay[1]CellLine:ParentalKellyandCDK12C1039FcellsConcentration:10-10000nMIncubationTime:72hoursResult:AntiproliferativeactivityofBSJ-4-116isindependentofthemutationalstatus,andthedegradercompoundsexhibitedimprovedGR50(growthrateinhibition)valuesinKellyCDK12C1039Fcellscomparedwiththeparentalcellline.WesternBlotAnalysis[1]CellLine:ParentalandCDK12C1039F(KellyCDK12CF)-expressingKellycellsConcentration:50?nMIncubationTime:6-24?hoursResult:LedtothesamelevelofCDK12proteinleveldecrease,regardlessofthemutationalstatusofthecellline.REFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].JiangB,etal.DiscoveryandresistancemechanismofaselectiveCDK12degrader.NatChemBiol.2021;17(6):675-683.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalappli