Publication — IRIC

Dual-function antiandrogen/HDACi hybrids based on enzalutamide and entinostat.

The combination of androgen receptor antagonists with histone deacetylase inhibitors (HDACi) has been shown to be more effective than antiandrogens alone in halting growth of prostate cancer cell lines. Here we have designed, synthesized and assessed a series of antiandrogen/HDACi hybrids by combining structural features of enzalutamide with either SAHA or entinostat. The hybrids are demonstrated to maintain bifunctionality using a fluorometric HDAC assay and a bioluminescence resonance energy transfer (BRET) antiandrogen assay. Antiproliferative assays showed that hybrids bearing o-aminoanilide-based HDACi motifs outperformed hydroxamic acid based HDACi’s. The hybrids demonstrated selectivity for epithelial cell lines vs. stromal cell lines, suggesting a potentially useful therapeutic window.

Publication date
novembre 9, 2021
Principal Investigators
Barrett RRG, Nash C, Diennet M, Cotnoir-White D, Doyle C, Mader S, Thomson AA, Gleason JL
PubMed reference
Bioorg Med Chem Lett 2021;55:128441
PubMed ID
Department of Chemistry, McGill University, 801 Sherbrooke W., Montreal, QC H3A 0B8, Canada.