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Journal of Shanghai University >

2018 , Vol. 24 >Issue 1: 126 - 133

DOI: https://doi.org/10.12066/j.issn.1007-2861.1757

Research Articles

Establishment of molecular-based high-throughout screening model for histone lysine methyltransferase DOT1L inhibitors

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  • 1. School of Life Sciences, Shanghai University, Shanghai 200444, China
    2. The National Center for Drug Screening, Shanghai 201203, China

Received date: 2016-03-21

  Online published: 2018-03-05

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Abstract

DOT1L is an epigenetic enzyme that can catalyze methyltransfer activity at histone 3 lysine 79 (H3K79). It is also found to be the first lysine methyltransferase without a SET domain. Research results show that methylation level of H3K79 can influence the expression of some genes, closely related to the development of acute myelocytic leukemia (AML). This work establishes a molecular-based high-throughout screening model for discovering novel DOT1L inhibitors. EPZ-5676 was used as positive control to optimize activity assay and ensure appropriate concentration of enzyme and substrate, and reaction time, etc. The assay was optimized, and the $Z'$-factor was about 0.54, indicating that a molecular-based high-throughout screening model for DOT1L inhibitors was successfully established.

Key words： disruptor of telomeric silencing 1-like (DOT1L); histone lysine methyltransferase; small molecule inhibitor; high-throughout screening (HTS)

Cite this article

XU Wei, SU Mingbo, ZHOU Yubo . Establishment of molecular-based high-throughout screening model for histone lysine methyltransferase DOT1L inhibitors[J]. Journal of Shanghai University, 2018 , 24(1) : 126 -133 . DOI: 10.12066/j.issn.1007-2861.1757

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