Design and synthesis of estrogen receptor degradation inducer based on a protein knockdown strategy

We designed and synthesized estrogen receptor (ER) degradation inducers 5, 6, and 7, which crosslink the ER and the cellular inhibitor of apoptosis protein 1 (cIAP1). Compounds 5, 6, and 7 induced cIAP1-mediated ubiquitylation of ERα resulting in its proteasomal degradation.

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Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2012-02, Vol.22 (4), p.1793-1796
Hauptverfasser:	Demizu, Yosuke, Okuhira, Keiichiro, Motoi, Hiromi, Ohno, Akiko, Shoda, Takuji, Fukuhara, Kiyoshi, Okuda, Haruhiro, Naito, Mikihiko, Kurihara, Masaaki
Format:	Artikel
Sprache:	eng
Schlagworte:	Antineoplastic Agents - pharmacology apoptosis Biological and medical sciences Breast Neoplasms Cell Line, Tumor chemistry Dose-Response Relationship, Drug Drug Design Estrogen receptor Estrogen Receptor alpha - metabolism estrogen receptors Female Humans Inhibitor of Apoptosis Proteins - metabolism Medical sciences Models, Biological Molecular Structure Pharmacology. Drug treatments Protein Binding Protein knockdown Receptors, Estrogen - metabolism Tamoxifen Ubiquitin-proteasome system Ubiquitination - drug effects
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Beschreibung
Zusammenfassung:	We designed and synthesized estrogen receptor (ER) degradation inducers 5, 6, and 7, which crosslink the ER and the cellular inhibitor of apoptosis protein 1 (cIAP1). Compounds 5, 6, and 7 induced cIAP1-mediated ubiquitylation of ERα resulting in its proteasomal degradation.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2011.11.086