SY-5609-CDK7-IN-3-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESY-5609Cat.No.:HY-138293CASNo.:2417302-07-7Synonyms:CDK7-IN-3分⼦式:C₂₃H₂₆F₃N₆OP分⼦量:490.46作⽤靶点:CDK;Apoptosis作⽤通路:CellCycle/DNADamage;Apoptosis储存⽅式:4°C,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen)溶解性数据体外实验DMSO:40mg/mL(81.56mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0389mL10.1945mL20.3890mL5mM0.4078mL2.0389mL4.0778mL10mM0.2039mL1.0195mL2.0389mL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(storedundernitrogen)。-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>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.10mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:4mg/mL(8.16mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥4mg/mL(8.16mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性SY-5609(CDK7-IN-3)⼀种⼝服有效的，⾼选择性，⾮共价的CDK7抑制剂，KD为0.065nM。SY-5609对CDK2(Ki=2600nM)，CDK9(Ki=960nM)，CDK12(Ki=870nM)具有较弱的抑制作⽤。SY-5609诱导肿瘤细胞凋亡并具有抗肿瘤活性。IC50&TargetCDK7CDK2CDK9CDK120.065nM(Kd)2600nM(Ki)960nM(Ki)870nM(Ki)体外研究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—您⾝边的抑制剂⼤师www.MedChemEIncubationTime:48hoursResult:InducedG2/Mcellcyclearrest.WesternBlotAnalysis[1]CellLine:HCC70cellsConcentration:25,50,100,250,500nMIncubationTime:6,24,48hoursResult:ResultedininhibitionofthephosphorylationofCDK2atThr160vialossofCAKfunctionfor24and48h.体内研究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