Discovery of Irreversible Inhibitors Targeting Histone Methyltrans-ferase, SMYD3

Discovery of Irreversible Inhibitors Targeting Histone Methyltrans-ferase, SMYD3
Title:
Discovery of Irreversible Inhibitors Targeting Histone Methyltrans-ferase, SMYD3
Other Titles:
ACS Medicinal Chemistry Letters
Keywords:
Publication Date:
23 May 2019
Citation:
ACS Med. Chem. Lett.2019, 10, 6, 978-984
Abstract:
SMYD3 is a histone methyltransferase that regulates gene transcription and its overexpression is associated with multiple human cancers. A novel class of tetrahydroacridine compounds which inhibit SMYD3 through a covalent mechanism of action is identified. Optimization of these irreversible inhibitors resulted in the discovery of 4-chloroquinolines, a new class of covalent warheads. Tool compound 29 exhibits high potency by inhibiting SMYD3’s enzymatic activity and showing anti-proliferative activity against HepG2 in 3D cell culture. Our findings suggest that covalent inhibition of SMYD3 may have an impact on SMYD3 biology by affecting expression levels and warrants further exploration.
License type:
PublisherCopyrights
Funding Info:
A*STAR Biomedical Research Council, Singapore
Description:
ISSN:
1948-5875
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