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Polyamine-based small molecule epigenetic modulators
Journal article   Peer reviewed

Polyamine-based small molecule epigenetic modulators

Shiv K. Sharma, Stuart Hazeldine, Michael L. Crowley, Allison Hanson, Ross Beattie, Sheeba Varghese, Thulani M. D. Senanayake, Aiko Hirata, Fusao Hirata, Yi Huang, …
MedChemComm, Vol.3(1), pp.14-21
01/01/2012
DOI: 10.1039/c1md00220a
PMCID: PMC3535317
PMID: 23293738
url
https://www.ncbi.nlm.nih.gov/pmc/articles/3535317View
Open Access

Abstract

Chromatin remodelling enzymes such as the histone deacetylases (HDACs) and histone demethylases such as lysine-specific demethylase 1 (LSD1) have been validated as targets for cancer drug discovery. Although a number of HDAC inhibitors have been marketed or are in human clinical trials, the search for isoform-specific HDAC inhibitors is an ongoing effort. In addition, the discovery and development of compounds targeting histone demethylases are in their early stages. Epigenetic modulators used in combination with traditional antitumor agents such as 5-azacytidine represent an exciting new approach to cancer chemotherapy. We have developed multiple series of HDAC inhibitors and LSD1 inhibitors that promote the re-expression of aberrantly silenced genes that are important in human cancer. The design, synthesis and biological activity of these analogues is described herein.
Biochemistry & Molecular Biology Chemistry, Medicinal Life Sciences & Biomedicine Pharmacology & Pharmacy Science & Technology

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