ReviewJournal of medicinal chemistry2013
A medicinal chemistry perspective for targeting histone H3 lysine-79 methyltransferase DOT1L.
Review in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 76 citations in OpenAlex.
- The effects of genetically determined plasma methyltransferases on digestive system cancers: a comprehensive bidirectional two-sample Mendelian randomization analysis.Discover oncology · 2025Article
- Synthesis, Structure-Activity Relationships, and Antitumor Activities of Quinoxiline-Containing Inhibitors of the Protein-Protein Interactions between Transcription Coactivator AF9/ENL and DOT1L/AF4.Journal of medicinal chemistry · 2025Article
- Design, synthesis and evaluation of pyrimidinobenzylamide and pyrimidinothiophenamide derivatives as inhibitors of DOT1L and related epigenetic targets DNMT3a, PRMT4 and other HMTs.RSC medicinal chemistry · 2025Article
- DOT1L protects against podocyte injury in diabetic kidney disease through phospholipase C-like 1.Cell communication and signaling : CCS · 2024Article
- Gain-of-function mutations in the catalytic domain ofScience advances · 2023Article
- A proteolysis-targeting chimera molecule selectively degrades ENL and inhibits malignant gene expression and tumor growth.Journal of hematology & oncology · 2022Article
- The Role and Mechanism of Lysine Methyltransferase and Arginine Methyltransferase in Kidney Diseases.Frontiers in pharmacology · 2022Review
- Selective Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibition by the SCH772984 Compound Attenuates In Vitro and In Vivo Inflammatory Responses and Prolongs Survival in Murine Sepsis Models.International journal of molecular sciences · 2021Article
- Synthetic lethality and synergetic effect: the effective strategies for therapy of IDH-mutated cancers.Journal of experimental & clinical cancer research : CR · 2021Review
- Non-canonical H3K79me2-dependent pathways promote the survival of MLL-rearranged leukemia.eLife · 2021Article
- Discovery of Potent Small-Molecule Inhibitors of MLL Methyltransferase.ACS medicinal chemistry letters · 2020Article
- DOT1L: a key target in normal chromatin remodelling and in mixed-lineage leukaemia treatment.Epigenetics · 2020Review
- Identification of DOT1L inhibitors by structure-based virtual screening adapted from a nucleoside-focused library.European journal of medicinal chemistry · 2020Article
- Targeting Histone Methyltransferase DOT1L by a Novel Psammaplin A Analog Inhibits Growth and Metastasis of Triple-Negative Breast Cancer.Molecular therapy oncolytics · 2019Article
- Rewiring the Epigenetic Networks inFrontiers in cell and developmental biology · 2019Review
- Disruptor of telomeric silencing 1-like (DOT1L): disclosing a new class of non-nucleoside inhibitors by means of ligand-based and structure-based approaches.Journal of computer-aided molecular design · 2018Article
- Inhibitors of Protein Methyltransferases and Demethylases.Chemical reviews · 2018Review
- Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach.ACS medicinal chemistry letters · 2017Article
- DNA Methylation Targeting: The DNMT/HMT Crosstalk Challenge.Biomolecules · 2017Review
- Metabolism, Biochemical Actions, and Chemical Synthesis of Anticancer Nucleosides, Nucleotides, and Base Analogs.Chemical reviews · 2016Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Histone H3 lysine79 (H3K79) methyltransferase DOT1L plays an important role in the activation and maintenance of gene transcription. It is essential for embryonic development as well as normal functions of the hematopoietic system, heart, and kidney in adults. DOT1L has been found to be a drug target for acute leukemia with mixed lineage leukemia (MLL) gene translocations. The rearranged onco-MLL can recruit DOT1L, causing aberrant H3K79 methylation, overexpression of leukemia relevant genes, and eventually leukemogenesis. Potent DOT1L inhibitors possess selective activity against this type of leukemia in cell-based and animal studies, with the most advanced compound being in clinical trials. In the medicinal chemistry point of view, we review the biochemistry, cancer biology, and current inhibitors of DOT1L, as well as biophysical (including X-ray crystallographic) investigation of DOT1L-inhibitor interactions. Potential future directions in the context of drug discovery and development targeting DOT1L are discussed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.