Publication — IRIC

Incorporation of histone deacetylase inhibitory activity into the core of tamoxifen - A new hybrid design paradigm.

Hybrid antiestrogen/histone deacetylase (HDAC) inhibitors were designed by appending zinc binding groups to the 4-hydroxystilbene core of 4-hydroxytamoxifen. The resulting hybrids were fully bifunctional, and displayed high nanomolar to low micromolar IC50 values against both the estrogen receptor α (ERα) and HDACs in vitro and in cell-based assays. The hybrids were antiproliferative against ER+ MCF-7 breast cancer cells, with hybrid 28b possessing an improved activity profile compared to either 4-hydroxytamoxifen or SAHA. Hybrid 28b displayed gene expression patterns that reflected both ERα and HDAC inhibition.

Publication date
August 15, 2018
Principal Investigators
Palermo AF, Diennet M, El Ezzy M, Williams BM, Cotnoir-White D, Mader S, Gleason JL
PubMed reference
Bioorg. Med. Chem. 2018;26(15):4428-4440
PubMed ID
Department of Chemistry, McGill University, 801 Sherbrooke W., Montreal, QC H3A 0B8, Canada.