» Articles » PMID: 33041512

Synthesis of Artificial Substrate Based on Inhibitor for Detecting LSD1 Activity

Overview
Specialty Biochemistry
Date 2020 Oct 12
PMID 33041512
Citations 1
Authors
Affiliations
Soon will be listed here.
Abstract

Lysine methylation is one of the most important modification, which is regulated by histone lysine methyltransferases and histone lysine demethylases. Lysine-specific demethylase 1 (LSD1) specifically demethylates mono- and dimethyl-lysine on histone H3 (H3K4Me/Me, H3K9Me/Me) to control chromatin structure, resulting in transcriptional repression or activation of target genes. Furthermore, LSD1 is overexpressed in various cancers. Therefore, LSD1 inhibitors would be not only potential therapeutic agents for cancers but also chemical tools to research biological significance of LSD1 in physiological and pathological events. However, known assay methods to date have some inherent drawbacks. The development of simple method in detecting LSD1 activity has been indispensable to identify useful inhibitors. In this study, we designed and synthesized artificial substrates based on inhibitors of LSD1 to examine LSD1 activity by an absorption increment.

Citing Articles

Enrichment of H3S28p and H3K9me2 Epigenetic Marks on Inflammatory-Associated Gene Promoters in Response to Severe Burn Injury.

Arias-Perez O, Escobedo-Tapia T, Cintora-Ahumada C, Leon-Solis L, Leyva-Garcia N, Arechaga-Ocampo E Life (Basel). 2025; 14(12.

PMID: 39768289 PMC: 11677237. DOI: 10.3390/life14121581.


Tertiary sulphonamide derivatives as dual acting small molecules that inhibit LSD1 and suppress tubulin polymerisation against liver cancer.

Ding L, Wei F, Wang N, Sun Y, Wang Q, Fan X J Enzyme Inhib Med Chem. 2021; 36(1):1563-1572.

PMID: 34281464 PMC: 8291071. DOI: 10.1080/14756366.2021.1917564.

References
1.
Yang C, Wang W, Liang J, Li G, Vellaisamy K, Wong C . A Rhodium(III)-Based Inhibitor of Lysine-Specific Histone Demethylase 1 as an Epigenetic Modulator in Prostate Cancer Cells. J Med Chem. 2017; 60(6):2597-2603. DOI: 10.1021/acs.jmedchem.7b00133. View

2.
Zhou C, Wu F, Lu L, Wei L, Pai E, Yao Y . Structure activity relationship and modeling studies of inhibitors of lysine specific demethylase 1. PLoS One. 2017; 12(2):e0170301. PMC: 5291514. DOI: 10.1371/journal.pone.0170301. View

3.
Huang J, Sengupta R, Espejo A, Lee M, Dorsey J, Richter M . p53 is regulated by the lysine demethylase LSD1. Nature. 2007; 449(7158):105-8. DOI: 10.1038/nature06092. View

4.
Schulte J, Lim S, Schramm A, Friedrichs N, Koster J, Versteeg R . Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy. Cancer Res. 2009; 69(5):2065-71. DOI: 10.1158/0008-5472.CAN-08-1735. View

5.
Prusevich P, Kalin J, Ming S, Basso M, Givens J, Li X . A selective phenelzine analogue inhibitor of histone demethylase LSD1. ACS Chem Biol. 2014; 9(6):1284-93. PMC: 4076021. DOI: 10.1021/cb500018s. View