ArticleJournal of medicinal chemistry2019
Discovery of a Novel Chemotype of Histone Lysine Methyltransferase EHMT1/2 (GLP/G9a) Inhibitors: Rational Design, Synthesis, Biological Evaluation, and Co-crystal Structure.
Article in Journal of medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
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- Regulation of BCL11A DNA binding and expression in human erythrocyte precursor HUDEP-2 cells.bioRxiv : the preprint server for biology · 2026Article
- Access to Pyrazolo[1,5-Organic letters · 2026Article
- Targeting Histone H3K9 Methyltransferase G9a as a Potential Therapeutic Strategy for Neuropsychiatric Disorders.Medicinal research reviews · 2025Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Design, synthesis and antitumor activity of 4-indazolylpyrimidine derivatives as EGFR inhibitors.Molecular diversity · 2025Article
- Epigenetic editing and epi-drugs: a combination strategy to simultaneously target KDM4 as a novel anticancer approach.Clinical epigenetics · 2025Article
- Unveiling New Triazoloquinoxaline-Based PROTACs Designed for the Selective Degradation of the ncBAF Chromatin Remodeling Subunit BRD9.Chemistry (Weinheim an der Bergstrasse, Germany) · 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
- Review
- Discovery of the First-in-Class G9a/GLP PROTAC Degrader.Journal of medicinal chemistry · 2024Article
- C2H2 Zinc Finger Transcription Factors Associated with Hemoglobinopathies.Journal of molecular biology · 2024Review
- Discovery of the First-in-class G9a/GLP PROTAC Degrader.bioRxiv : the preprint server for biology · 2024Article
- Insights into the Role of Histone Methylation in Brain Aging and Potential Therapeutic Interventions.International journal of molecular sciences · 2023Review
- Epigenetic Modulators as Therapeutic Agents in Cancer.International journal of molecular sciences · 2023Review
- Article
- Medicinal Chemistry of Anti-HIV-1 Latency Chemotherapeutics: Biotargets, Binding Modes and Structure-Activity Relationship Investigation.Molecules (Basel, Switzerland) · 2022Review
- An Optimized Microscale Thermophoresis Method for High-Throughput Screening of DNA Methyltransferase 2 Ligands.ACS pharmacology & translational science · 2022Article
- Discovery of Benzo[d]imidazole-6-sulfonamides as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with Selectivity for the First Bromodomain.ChemMedChem · 2022Article
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Authors and funding
14 authors.
Funding
Abstract
Since the discovery of compound BIX01294 over 10 years ago, only a very limited number of nonquinazoline inhibitors of H3K9-specific methyltransferases G9a and G9a-like protein (GLP) have been reported. Herein, we report the identification of a novel chemotype for G9a/GLP inhibitors, based on the underinvestigated 2-alkyl-5-amino- and 2-aryl-5-amino-substituted 3 H-benzo[ e][1,4]diazepine scaffold. Our research efforts resulted in the identification 12a (EML741), which not only maintained the high in vitro and cellular potency of its quinazoline counterpart, but also displayed improved inhibitory potency against DNA methyltransferase 1, improved selectivity against other methyltransferases, low cell toxicity, and improved apparent permeability values in both parallel artificial membrane permeability assay (PAMPA) and blood-brain barrier-specific PAMPA, and therefore might potentially be a better candidate for animal studies. Finally, the co-crystal structure of GLP in complex with 12a provides the basis for the further development of benzodiazepine-based G9a/GLP inhibitors.
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