ArticlePloS one2015
The Histone Methyltransferase Inhibitor A-366 Uncovers a Role for G9a/GLP in the Epigenetics of Leukemia.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 94 citations in OpenAlex.
- Targeting Histone H3K9 Methyltransferase G9a as a Potential Therapeutic Strategy for Neuropsychiatric Disorders.Medicinal research reviews · 2025Review
- Dual targeting of G9a and DNMTs induces antitumor effects in multiple myeloma.Blood advances · 2025Article
- G9a an Epigenetic Therapeutic Strategy for Neurodegenerative Conditions: From Target Discovery to Clinical Trials.Medicinal research reviews · 2025Review
- Targeting SETDB1 in cancer and immune regulation: Potential therapeutic strategies in cancer.The Kaohsiung journal of medical sciences · 2025Review
- Phenomics-Based Discovery of Novel Orthosteric Choline Kinase Inhibitors.Angewandte Chemie (International ed. in English) · 2025Article
- Immune-modulatory effects of Spindlin-1 inhibitors.Clinical and experimental immunology · 2025Article
- H3K9 post-translational modifications regulate epiblast/primitive endoderm specification in rabbit blastocysts.Epigenetics & chromatin · 2025Article
- Pharmacological targeting of CBX7 alters the epigenetic landscape and induces differentiation of leukemic cells.Blood neoplasia · 2024Article
- How CBX proteins regulate normal and leukemic blood cells.FEBS letters · 2024Review
- GLP and G9a histone methyltransferases as potential therapeutic targets for lymphoid neoplasms.Cancer cell international · 2024Review
- Review
- SETDB1 as a cancer target: challenges and perspectives in drug design.RSC medicinal chemistry · 2024Review
- Inhibition of EHMT1/2 rescues synaptic damage and motor impairment in a PD mouse model.Cellular and molecular life sciences : CMLS · 2024Article
- Therapeutic targeting Tudor domains in leukemia via CRISPR-Scan Assisted Drug Discovery.Science advances · 2024Article
- Tumor-suppressive functions of protein lysine methyltransferases.Experimental & molecular medicine · 2023Review
- Loss of renal tubular G9a benefits acute kidney injury by lowering focal lipid accumulation via CES1.EMBO reports · 2023Article
- Dual inhibition of EZH2 and G9A/GLP histone methyltransferases by HKMTI-1-005 promotes differentiation of acute myeloid leukemia cells.Frontiers in cell and developmental biology · 2023Article
- De novo methylation of histone H3K23 by the methyltransferases EHMT1/GLP and EHMT2/G9a.Epigenetics & chromatin · 2022Article
- Inhibition of the CtBP complex and FBXO11 enhances MHC class II expression and anti-cancer immune responses.Cancer cell · 2022Article
- Single-cell multiomics sequencing reveals the reprogramming defects in embryos generated by round spermatid injection.Science advances · 2022Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone methyltransferases are epigenetic regulators that modify key lysine and arginine residues on histones and are believed to play an important role in cancer development and maintenance. These epigenetic modifications are potentially reversible and as a result this class of enzymes has drawn great interest as potential therapeutic targets of small molecule inhibitors. Previous studies have suggested that the histone lysine methyltransferase G9a (EHMT2) is required to perpetuate malignant phenotypes through multiple mechanisms in a variety of cancer types. To further elucidate the enzymatic role of G9a in cancer, we describe herein the biological activities of a novel peptide-competitive histone methyltransferase inhibitor, A-366, that selectively inhibits G9a and the closely related GLP (EHMT1), but not other histone methyltransferases. A-366 has significantly less cytotoxic effects on the growth of tumor cell lines compared to other known G9a/GLP small molecule inhibitors despite equivalent cellular activity on methylation of H3K9me2. Additionally, the selectivity profile of A-366 has aided in the discovery of a potentially important role for G9a/GLP in maintenance of leukemia. Treatment of various leukemia cell lines in vitro resulted in marked differentiation and morphological changes of these tumor cell lines. Furthermore, treatment of a flank xenograft leukemia model with A-366 resulted in growth inhibition in vivo consistent with the profile of H3K9me2 reduction observed. In summary, A-366 is a novel and highly selective inhibitor of G9a/GLP that has enabled the discovery of a role for G9a/GLP enzymatic activity in the growth and differentiation status of leukemia cells.
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