Access Type
Open Access Thesis
Date of Award
1-1-2011
Degree Type
Thesis
Degree Name
M.S.
Department
Pharmaceutical Sciences
First Advisor
Patrick M. Woster
Second Advisor
Timothy L. Stemmler
Abstract
The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 over expression is thought to contribute to the development of cancer. We recently reported a series of (bis)guanidines and (bis)biguanides that are potent inhibitors of LSD1, and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a new series of isosteres that are also potent inhibitors of LSD1. These compounds induce increases in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in Calu-6 lung carcinoma cells. In addition, these analogues increase cellular levels of secreted frizzle-related proteins (SFRP) 2 and 5, and transcription factor GATA4. These compounds represent an important new series of epigenetic modulators with the potential for use as antitumor agents.
Recommended Citation
Crowley, Michael, "Novel inhibitors of lysine specific demethylase 1 as epigenetic modulators" (2011). Wayne State University Theses. 132.
https://digitalcommons.wayne.edu/oa_theses/132