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Updated: Apr 21, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
β-Lactam estrogen receptor antagonists and a dual-targeting estrogen receptor/tubulin ligand
Niamh M O'Boyle1, Jade K Pollock, Miriam Carr
1School of Pharmacy and Pharmaceutical Sciences, Centre for Synthesis and Chemical Biology and ‡School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College , 152-160 Pearse Street, Dublin 2, Ireland.
Abstract:
Twelve novel β-lactams were synthesized and their antiproliferative effects and binding affinity for the predominant isoforms of the estrogen receptor (ER), ERα and ERβ, were determined. β-Lactams 23 and 26 had the strongest binding affinities for ERα (IC50 values: 40 and 8 nM, respectively) and ERβ (IC50 values: 19 and 15 nM). β-Lactam 26 was the most potent in antiproliferative assays using MCF-7 breast cancer cells, and further biochemical analysis showed that it caused accumulation of cells in G2/M phase (mitotic blockade) and depolymerization of tubulin in MCF-7 cells. Compound 26 also induced apoptosis and downregulation of the expression of pro-survival proteins Bcl-2 and Mcl-1. Computational modeling predicted binding preferences for the dual ER/tubulin ligand 26. This series is an important addition to the known pool of ER antagonists and β-lactam 26 is the first reported compound that has dual-targeting properties for both the ER and tubulin.
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