Selective CDK6 degradation mediated by cereblon, VHL, and novel IAP-recruiting PROTACs
作者: Niall A. AndersonJenni CryanAdil AhmedHan DaiGrant A. McGonagleChristine RozierAndrew B. Benowitz
作者单位: 1Medicine Design, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom
刊名: Bioorganic & Medicinal Chemistry Letters, 2020, Vol.30 (9)
来源数据库: Elsevier Journal
DOI: 10.1016/j.bmcl.2020.127106
关键词: CDK4CDK6PROTACPalbociclib
原始语种摘要: Abstract(#br)Inhibitors of CDK4 and CDK6 have emerged as important FDA-approved treatment options for breast cancer patients. The properties and pharmacology of CDK4/6 inhibitor medicines have been extensively profiled, and investigations into the degradation of these targets via a PROTAC strategy have also been reported. PROTACs are a novel class of small-molecules that offer the potential for differentiated pharmacology compared to traditional inhibitors by redirecting the cellular ubiquitin–proteasome system to degrade target proteins of interest. We report here the preparation of palbociclib-based PROTACs that incorporate binders for three different E3 ligases, including a novel IAP-binder, which effectively degrade CDK4 and CDK6 in cells. In addition, we show that the...
全文获取路径: Elsevier  (合作)
影响因子:2.338 (2012)

  • degradation 减嚣夷酌
  • novel 长篇小说