pp 1-35 | Cite as

Lysine Methyltransferases and Their Inhibitors

  • Giulia Stazi
  • Clemens Zwergel
  • Sergio ValenteEmail author
Part of the Topics in Medicinal Chemistry book series


Since 2000, the histone methyltransferases that catalyze the methylation of a number of histone and nonhistone substrates have been discovered.

A growing body of literature is indicating that lysine methyltransferases (KMTs) play a crucial role for transcriptional regulation and are involved in cancer and various other human diseases, thus being of high interest as potential therapeutic targets.

In this book chapter, we highlight the discovery, characterization, and application of selective KMT inhibitors, useful for dissecting their physiological functions as well as their disease implications.

Over the past decade, there has been an impressive progress regarding the KMT inhibitor discovery, especially conjugating the research interest with the available and novel techniques including new assay methods, high-throughput screening, structural biology, and medicinal chemistry approaches. Our goal is to point out herein key advances, challenges, possible future opportunities, and directions, regarding KMT modulation in a preclinical and clinical setting.


Cancer Chromatin DOT1L Epigenetic modulators EZH2 G9a Lysine methyltransferases SETs SUVs 



5-Hydroxytryptamine receptor 2A


Acute myeloid leukemia


ASH2 like histone lysine methyltransferase complex subunit


Coactivator-associated arginine methyltransferase 1


Diffuse large B-cell lymphoma


DNA methyltransferase


DNA methyltransferase inhibitor


Disruptor of telomeric silencing 1-like


Embryonic ectoderm development


Euchromatin histone methyltransferase 1 (see also GLP)


Euchromatin histone methyltransferase 2 (see also G9a)


Estrogen receptor alpha


Enhancer of zeste homologue 1


Enhancer of zeste homologue 2


Fluorescence polarization


Euchromatic histone-lysine N-methyltransferase 2 (EHMT2)


G9a-like protein (EHMT1)


G protein-coupled receptor


Histamine receptor 1


Lysine 9 of histone 3


Demethylated lysine 9 of histone 3


Hemoglobin F


Colon colorectal carcinoma cell line


Histone deacetylase inhibitors


Human embryonic kidney cell line


Human leukemia cell line


Heat shock protein 90


High-throughput screening


Intrauterine growth restriction


Lymphoma cell line


Lysine methyltransferases


Prostate adenocarcinoma cells


Mitogen-activated protein kinase kinase kinase 2


Non-tumorigenic epithelial cell line


Breast cancer cell line


Human breast cancer cell line


Mixed-lineage leukemia


Mechanism of action

MV4–11 (MLL-AF4), MOLM-13 (MLL-AF9), and THP1 (MLL-AF9)

MLL-rearranged cell lines


Myeloid translocation protein-8, Nervy, and DEAF-1


Poly(ADP-ribose)-polymerase 1


Prostate cancer cell line


Proliferating cell nuclear antigen


Physical-chemical (properties)


Protein lysine methyltransferases


Promyelocytic leukemia protein nuclear bodies


Protein methyltransferases


Peroxisome proliferator-activated receptor gamma


Protein-protein interaction


Polycomb-repressive complex 2


Protein arginine methyltransferases


Prader-Willi syndrome




Retinoblastoma-binding protein 5


Response element II-binding protein


RNA methyltransferases


S-adenosyl homocysteine




Structure-activity relationship


Sickle cell disease


Small cell lung cancer


Nuclear proto-oncogene


SET domain containing 2 histone methyltransferase


SET domain containing 7 histone methyltransferase


SET domain containing 8 histone methyltransferase


SET domain bifurcated 1


SET and MYND domain-containing


Breast cancer cell line


Histone-lysine N-methyltransferase


Subunit polycomb-repressive complex 2


Osteosarcoma cell line


Histiocytic lymphoma cell line


Vascular endothelial growth factor receptor 1


WD repeat-containing protein 5


Wild type


Compliance with Ethical Standards

Conflict of Interest: The authors declare no conflict of interest.

Ethical Approval: This article does not contain any studies with human participants or animals performed by any of the authors.


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© Springer Nature Switzerland AG  2019

Authors and Affiliations

  1. 1.Department of Drug Chemistry and TechnologiesSapienza University of RomeRomeItaly

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