ArticleJournal of medicinal chemistry2018
Development of Mithramycin Analogues with Increased Selectivity toward ETS Transcription Factor Expressing Cancers.
Article in Journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 30 citations in OpenAlex.
- Crystal Structure of Trabectedin-DNA Complex.Journal of molecular biology · 2026Article
- Nonlinear Mixed-Effects Modeling to Characterize the Pharmacokinetics of a Novel Mithramycin Analogue for Ewing Sarcoma in Mice.Research square · 2026Article
- Preclinical Pharmacokinetic Evaluation of Mithramycin and Mithramycin SA Tryptophan-Conjugated Analog.Pharmaceutics · 2025Article
- The Position of Indole Methylation Controls the Structure, DNA Binding, and Cellular Functions of Mithramycin SA-Trp Analogues.Chembiochem : a European journal of chemical biology · 2025Article
- Total synthesis of asperdinones B, C, D, E and terezine D.Beilstein journal of organic chemistry · 2025Article
- Poly(ADP-ribose) Polyremase-1 (PARP-1) Inhibition: A Promising Therapeutic Strategy for ETS-Expressing Tumours.International journal of molecular sciences · 2023Review
- Targeted Therapy for EWS-FLI1 in Ewing Sarcoma.Cancers · 2023Review
- Mithplatins: Mithramycin SA-Pt(II) Complex Conjugates for the Treatment of Platinum-Resistant Ovarian Cancers.ChemMedChem · 2023Article
- Interleukin-10 suppression enhances T-cell antitumor immunity and responses to checkpoint blockade in chronic lymphocytic leukemia.Leukemia · 2021Article
- Allosteric interference in oncogenic FLI1 and ERG transactions by mithramycins.Structure (London, England : 1993) · 2021Article
- Review
- Mithramycin 2'-Oximes with Improved Selectivity, Pharmacokinetics, and Ewing Sarcoma Antitumor Efficacy.Journal of medicinal chemistry · 2020Article
- Discrimination between G/C Binding Sites by Olivomycin A Is Determined by Kinetics of the Drug-DNA Interaction.International journal of molecular sciences · 2020Article
- Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis.Angewandte Chemie (International ed. in English) · 2020Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Mithramycin A (1) was identified as the top potential inhibitor of the aberrant ETS transcription factor EWS-FLI1, which causes Ewing sarcoma. Unfortunately, 1 has a narrow therapeutic window, compelling us to seek less toxic and more selective analogues. Here, we used MTMSA (2) to generate analogues via peptide coupling and fragment-based drug development strategies. Cytotoxicity assays in ETS and non-ETS dependent cell lines identified two dipeptide analogues, 60 and 61, with 19.1- and 15.6-fold selectivity, respectively, compared to 1.5-fold for 1. Importantly, the cytotoxicity of 60 and 61 is <100 nM in ETS cells. Molecular assays demonstrated the inhibitory capacity of these analogues against EWS-FLI1 mediated transcription in Ewing sarcoma. Structural analysis shows that positioning the tryptophan residue in a distal position improves selectivity, presumably via interaction with the ETS transcription factor. Thus, these analogues may present new ways to target transcription factors for clinical use.
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.