| Literature DB >> 26175415 |
Helai P Mohammad1, Kimberly N Smitheman1, Chandrashekhar D Kamat2, David Soong1, Kelly E Federowicz1, Glenn S Van Aller1, Jess L Schneck3, Jeffrey D Carson3, Yan Liu1, Michael Butticello1, William G Bonnette3, Shelby A Gorman1, Yan Degenhardt1, Yuchen Bai1, Michael T McCabe1, Melissa B Pappalardi1, Jiri Kasparec1, Xinrong Tian1, Kenneth C McNulty1, Meagan Rouse1, Patrick McDevitt3, Thau Ho3, Michelle Crouthamel1, Timothy K Hart4, Nestor O Concha3, Charles F McHugh1, William H Miller1, Dashyant Dhanak1, Peter J Tummino1, Christopher L Carpenter1, Neil W Johnson1, Christine L Hann2, Ryan G Kruger5.
Abstract
Epigenetic dysregulation has emerged as an important mechanism in cancer. Alterations in epigenetic machinery have become a major focus for targeted therapies. The current report describes the discovery and biological activity of a cyclopropylamine containing inhibitor of Lysine Demethylase 1 (LSD1), GSK2879552. This small molecule is a potent, selective, orally bioavailable, mechanism-based irreversible inactivator of LSD1. A proliferation screen of cell lines representing a number of tumor types indicated that small cell lung carcinoma (SCLC) is sensitive to LSD1 inhibition. The subset of SCLC lines and primary samples that undergo growth inhibition in response to GSK2879552 exhibit DNA hypomethylation of a signature set of probes, suggesting this may be used as a predictive biomarker of activity.Entities:
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Year: 2015 PMID： 26175415 DOI： 10.1016/j.ccell.2015.06.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743