Molecular Design, Synthesis, and Evaluation of SNIPER(ER) That Induces Proteasomal Degradation of ERα
Manipulation of protein stability using small molecules has a great potential for both basic research and clinical therapy. Based on our protein knockdown technology, we recently developed a novel small molecule SNIPER(ER) that targets the estrogen receptor alpha (ERα) for degradation via the ubiquitin–proteasome system. This chapter describes the design and synthesis of SNIPER(ER) compounds, and methods for the evaluation of their activity in cellular system.
Key wordsEstrogenreceptor SNIPER Proteinknockdown Ubiquitin–proteasome system Cell death
This study was supported by Grants-in Aid for Scientific Research from the Japan Society for the Promotion of Science (to M.N., K.O., and N.O.) and by Research Fund from Japan Health Sciences Foundation. We are grateful to Cancer Science, Japanese Cancer Association and John Wiley & Sons Ltd. for allowing the reproduction of figures published in .
- 8.Osborne CK, Pippen J, Jones SE et al (2002) Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol 20:3386–3395CrossRefPubMedGoogle Scholar