Document Report Card
Basic Information
ID: ALA4229504
Journal: Bioorg Med Chem
Title: Incorporation of histone deacetylase inhibitory activity into the core of tamoxifen - A new hybrid design paradigm.
Authors: Palermo AF, Diennet M, El Ezzy M, Williams BM, Cotnoir-White D, Mader S, Gleason JL.
Abstract: 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.
CiteXplore: 30078609