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

Yosuke Demizu; Keiichiro Okuhira; Hiromi Motoi; Akiko Ohno; Takuji Shoda; Kiyoshi Fukuhara; Haruhiro Okuda; Mikihiko Naito; Masaaki Kurihara

doi:10.1016/j.bmcl.2011.11.086

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

Bioorg Med Chem Lett. 2012 Feb 15;22(4):1793-6. doi: 10.1016/j.bmcl.2011.11.086. Epub 2011 Nov 28.

Authors

Yosuke Demizu¹, Keiichiro Okuhira, Hiromi Motoi, Akiko Ohno, Takuji Shoda, Kiyoshi Fukuhara, Haruhiro Okuda, Mikihiko Naito, Masaaki Kurihara

Affiliation

¹ Division of Organic Chemistry, National Institute of Health Sciences, Tokyo, Japan.

PMID: 22277276
DOI: 10.1016/j.bmcl.2011.11.086

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology
Breast Neoplasms
Cell Line, Tumor
Dose-Response Relationship, Drug
Drug Design*
Estrogen Receptor alpha / metabolism
Female
Humans
Inhibitor of Apoptosis Proteins / metabolism*
Models, Biological
Molecular Structure
Protein Binding
Receptors, Estrogen / metabolism*
Ubiquitination / drug effects

Substances

Antineoplastic Agents
ESR1 protein, human
Estrogen Receptor alpha
Inhibitor of Apoptosis Proteins
Receptors, Estrogen