| Literature DB >> 31223458 |
Chuhui Huang1, Si Si Liew1, Grace R Lin1, Anders Poulsen1, Melgious J Y Ang1, Brian C S Chia1, Sin Yin Chew1, Zekui P Kwek1, John L K Wee1, Esther H Ong1, Priya Retna1, Nithya Baburajendran1, Rong Li1, Weixuan Yu1, Xiaoying Koh-Stenta1, Anna Ngo1, Sravanthy Manesh1, Justina Fulwood1, Zhiyuan Ke1, Hwa Hwa Chung1, Sugunavathi Sepramaniam1, Xin Hui Chew1, Nurul Dinie1, May Ann Lee1, Yun Shan Chew1, Choon Bing Low1, Vishal Pendharkar1, Vithya Manoharan1, Susmitha Vuddagiri1, Kanda Sangthongpitag1, Joma Joy1, Alex Matter1, Jeffrey Hill1, Thomas H Keller1, Klement Foo1.
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 antiproliferative 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 this warrants further exploration.Entities:
Year: 2019 PMID： 31223458 PMCID： PMC6580565 DOI： 10.1021/acsmedchemlett.9b00170
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345