title: Molecular Design, Synthesis, and Evaluation of SNIPER(ER) That Induces Proteasomal Degradation of ERα.
abstract: 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.
authors.affiliation: Division of Biochemistry and Molecular Biology, National Institute of Health Sciences, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Okuhira
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Demizu
authors.affiliation: Division of Biochemistry and Molecular Biology, National Institute of Health Sciences, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Division of Biochemistry and Molecular Biology, National Institute of Health Sciences, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Nobumichi
authors.initials: N
authors.lastname: Ohoka
authors.affiliation: Division of Biochemistry and Molecular Biology, National Institute of Health Sciences, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Norihito
authors.initials: N
authors.lastname: Shibata
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kurihara
authors.affiliation: Division of Biochemistry and Molecular Biology, National Institute of Health Sciences, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan. miki-naito@nihs.go.jp.
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Naito
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D015195:Drug Design; D047628:Estrogen Receptor alpha / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D055550:Protein Stability; D059748:Proteolysis; D013194:Staining and Labeling; D013329:Structure-Activity Relationship; D013997:Time Factors; D054875:Ubiquitination; D057188:Workflow
chemical_list: D000970:Antineoplastic Agents; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D046988:Proteasome Endopeptidase Complex
keywords: Cell death; Estrogen receptor; Protein knockdown; SNIPER; Ubiquitin–proteasome system