ArticleJournal of computer-aided molecular design2018
Disruptor of telomeric silencing 1-like (DOT1L): disclosing a new class of non-nucleoside inhibitors by means of ligand-based and structure-based approaches.
Article in Journal of computer-aided molecular design, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 20 citations in OpenAlex.
- Combined computational and classical medicinal chemistry procedure to disclose novel pyrrole-based compounds as potential antituberculosis agents.Journal of computer-aided molecular design · 2026Article
- The Role of Histone Methylation in Heart Failure: Epigenetic Mechanisms and Therapeutic Perspectives.Drug design, development and therapy · 2026Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Epigenetic Regulation in Myocardial Fibroblasts and Its Impact on Cardiovascular Diseases.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Therapeutic Potential and Activity Modulation of the Protein Lysine Deacylase Sirtuin 5.Journal of medicinal chemistry · 2022Review
- Ligand-based and structure-based studies to develop predictive models for SARS-CoV-2 main protease inhibitors through the 3d-qsar.com portal.Journal of computer-aided molecular design · 2022Article
- A novel screening strategy to identify histone methyltransferase inhibitors reveals a crosstalk between DOT1L and CARM1.RSC chemical biology · 2022Article
- Targeting the histone H3 lysine 79 methyltransferase DOT1L in MLL-rearranged leukemias.Journal of hematology & oncology · 2022Review
- Histone Methyltransferase DOT1L as a Promising Epigenetic Target for Treatment of Solid Tumors.Frontiers in genetics · 2022Review
- Recent progress on cheminformatics approaches to epigenetic drug discovery.Drug discovery today · 2020Review
- QSPR study on the polyacrylate-water partition coefficients of hydrophobic organic compounds.Environmental science and pollution research international · 2020Article
- Identification of DOT1L inhibitors by structure-based virtual screening adapted from a nucleoside-focused library.European journal of medicinal chemistry · 2020Article
- Dissecting the role of novel EZH2 inhibitors in primary glioblastoma cell cultures: effects on proliferation, epithelial-mesenchymal transition, migration, and on the pro-inflammatory phenotype.Clinical epigenetics · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
Chemical inhibition of chromatin-mediated signaling involved proteins is an established strategy to drive expression networks and alter disease progression. Protein methyltransferases are among the most studied proteins in epigenetics and, in particular, disruptor of telomeric silencing 1-like (DOT1L) lysine methyltransferase plays a key role in MLL-rearranged acute leukemia Selective inhibition of DOT1L is an established attractive strategy to breakdown aberrant H3K79 methylation and thus overexpression of leukemia genes, and leukemogenesis. Although numerous DOT1L inhibitors have been several structural data published no pronounced computational efforts have been yet reported. In these studies a first tentative of multi-stage and LB/SB combined approach is reported in order to maximize the use of available data. Using co-crystallized ligand/DOT1L complexes, predictive 3-D QSAR and COMBINE models were built through a python implementation of previously reported methodologies. The models, validated by either modeled or experimental external test sets, proved to have good predictive abilities. The application of these models to an internal library led to the selection of two unreported compounds that were found able to inhibit DOT1L at micromolar level. To the best of our knowledge this is the first report of quantitative LB and SB DOT1L inhibitors models and their application to disclose new potential epigenetic modulators.
Indexed as
Identifiers
What OpenQuestion holds
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.