Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESY-5609Cat.No.:HY-138293CASNo.:2417302-07-7Synonyms:CDK7-IN-3分?式:C??H??F?N?OP分?量:490.46作?靶點:CDK;Apoptosis作?通路:CellCycle/DNADamage;Apoptosis儲存?式:4°C,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen)溶解性數據體外實驗DMSO:40mg/mL(81.56mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.0389mL10.1945mL20.3890mL5mM0.4078mL2.0389mL4.0778mL10mM0.2039mL1.0195mL2.0389mL請根據產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，避免反復凍融造成的產品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month(storedundernitrogen)。-80°C儲存時，請在6個?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?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：(為保證實驗結果的可靠性，澄的儲備液可以根據儲存條件，適當保存；體內實驗的?作液，建議您現?現配，當天使?；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沉淀、析出現象，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:≥2.5mg/mL(5.10mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:4mg/mL(8.16mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥4mg/mL(8.16mM);ClearsolutionBIOLOGICALACTIVITY?物活性SY-5609(CDK7-IN-3)?種?服有效的，?選擇性，?共價的CDK7抑制劑，KD為0.065nM。SY-5609對CDK2(Ki=2600nM)，CDK9(Ki=960nM)，CDK12(Ki=870nM)具有較弱的抑制作?。SY-5609誘導腫瘤細胞凋亡并具有抗腫瘤活性。IC50&TargetCDK7CDK2CDK9CDK120.065nM(Kd)2600nM(Ki)960nM(Ki)870nM(Ki)體外研究SY-5609(0.01-10000nM;72hours)demonstratesstrongantiproliferativeeffectsintriplenegativebreastcancer(TNBC)andovarian(OVA)cancercells[1].SY-5609(100-500nM;48,72hours)inducesapoptosis[1].SY-5609(100-500nM;48hours)inducesG2/McellcyclearrestinHCC70cells[1].SY-5609(25-500nM;6-48hours)resultsininhibitionofthephosphorylationofCDK2atThr160vialossofCAKfunctionfor24and48h[1].SY-5609(compound101;126.4pM-4μM;72hours)hasanEC50of5.6nMinHCC70cellline[2].CellProliferationAssay[1]CellLine:HCC70,MDA-MB453,COV504,A2780,OVCAR3,CAOV3cellsConcentration:0.01-10000nMIncubationTime:72hoursResult:DemonstratedstrongantiproliferativeeffectswithIC50of1-6nM.ApoptosisAnalysis[1]CellLine:HCC70,MDA-MB-468,CAOV3andOVCAR3cellsConcentration:100,250,500nMIncubationTime:48and72hoursResult:Inducedapoptosis.CellCycleAnalysis[1]CellLine:HCC70cellsConcentration:100,250,500nM2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:48hoursResult:InducedG2/Mcellcyclearrest.WesternBlotAnalysis[1]CellLine:HCC70cellsConcentration:25,50,100,250,500nMIncubationTime:6,24,48hoursResult:ResultedininhibitionofthephosphorylationofCDK2atThr160vialossofCAKfunctionfor24and48h.體內研究SY-5609(2mg/kg/day;orally;for21days)inducestumorregressionoverthe21-daydosingperiod[1].Dailyoraldosingof2mg/kgSY-5609inmiceprovidedaplasmaexposureof261.28ngh/mLwithaCmaxof50.67ng/mL(103nM)andaneliminationhalf-lifeof3.33h[1].AnimalModel:Six-to-eight-week-oldBalb/cnudefemalemicewithHCC70cellline[1]Dosage:2mg/kgAdministration:Orally;daily;for21daysResult:Inducedtumorregressionoverthe21-daydosingperiodandwaswelltolerated.Noregrowthoftumorwasobservedouttoday28.REFERENCES[1].MichaelBradley,etal.Inhibitorsofcyclin-dependentkinase7(cdk7).WO2020093011A1.[2].JasonJMarineau,etal.DiscoveryofSY-5609:ASelective,NoncovalentInhibitorofCDK7.JMedChem.2021Nov2.McePdfHeightCaution:Product