ArticleBioorganic & medicinal chemistry2015
Structure-activity study for (bis)ureidopropyl- and (bis)thioureidopropyldiamine LSD1 inhibitors with 3-5-3 and 3-6-3 carbon backbone architectures.
Article in Bioorganic & medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
What it found
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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.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Comparative analysis for optimal LSD1 inhibitors evaluation techniques: pros and cons.Journal of pharmaceutical analysis · 2026Review
- Lysine-Specific Demethylase 1 Inhibitors: A Comprehensive Review Utilizing Computer-Aided Drug Design Technologies.Molecules (Basel, Switzerland) · 2024Review
- Investigation of Newly Synthesized Bis-Acyl-Thiourea Derivatives of 4-Nitrobenzene-1,2-Diamine for Their DNA Binding, Urease Inhibition, and Anti-Brain-Tumor Activities.Molecules (Basel, Switzerland) · 2023Article
- Targeting the LSD1/KDM1 Family of Lysine Demethylases in Cancer and Other Human Diseases.Advances in experimental medicine and biology · 2023Review
- A state-of-the-art review on LSD1 and its inhibitors in breast cancer: Molecular mechanisms and therapeutic significance.Frontiers in pharmacology · 2022Review
- Histone lysine specific demethylase 1 inhibitors.RSC medicinal chemistry · 2020Review
- Exploration of 5-cyano-6-phenylpyrimidin derivatives containing an 1,2,3-triazole moiety as potent FAD-based LSD1 inhibitors.Acta pharmaceutica Sinica. B · 2020Article
- Epigenetic Reexpression of Hemoglobin F Using Reversible LSD1 Inhibitors: Potential Therapies for Sickle Cell Disease.ACS omega · 2020Article
- Macrocyclic Peptides Uncover a Novel Binding Mode for Reversible Inhibitors of LSD1.ACS omega · 2020Article
- Dual inhibitors of LSD1 and spermine oxidase.MedChemComm · 2019Article
- Polyamine metabolism and cancer: treatments, challenges and opportunities.Nature reviews. Cancer · 2018Review
- Inhibition of FAD-dependent lysine-specific demethylases by chiral polyamine analogues.RSC advances · 2018Article
- Cyclic peptide inhibitors of lysine-specific demethylase 1 with improved potency identified by alanine scanning mutagenesis.European journal of medicinal chemistry · 2018Article
- Inhibitors of Protein Methyltransferases and Demethylases.Chemical reviews · 2018Review
- Structural insight into inhibitors of flavin adenine dinucleotide-dependent lysine demethylases.Epigenetics · 2017Review
- Functional interaction of histone deacetylase 5 (HDAC5) and lysine-specific demethylase 1 (LSD1) promotes breast cancer progression.Oncogene · 2017Article
- Histone Lysine Demethylase Inhibitors.Cold Spring Harbor perspectives in medicine · 2017Review
- Targeting polyamine metabolism for cancer therapy and prevention.The Biochemical journal · 2016Review
- Antibacterial Diamines Targeting Bacterial Membranes.Journal of medicinal chemistry · 2016Article
- LSD1 Histone Demethylase Assays and Inhibition.Methods in enzymology · 2016Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Methylation at specific histone lysine residues is a critical post-translational modification that alters chromatin architecture, and dysregulated lysine methylation/demethylation is associated with the silencing of tumor suppressor genes. The enzyme lysine-specific demethylase 1 (LSD1) complexed to specific transcription factors catalyzes the oxidative demethylation of mono- and dimethyllysine 4 of histone H3 (H3K4me and H3K4me2, respectively). We have previously reported potent (bis)urea and (bis)thiourea LSD1 inhibitors that increase cellular levels of H3K4me and H3K4me2, promote the re-expression of silenced tumor suppressor genes and suppress tumor growth in vitro. Here we report the design additional (bis)urea and (bis)thiourea LSD1 inhibitors that feature 3-5-3 or 3-6-3 carbon backbone architectures. Three of these compounds displayed single-digit IC50 values in a recombinant LSD1 assay. In addition, compound 6d exhibited an IC50 of 4.2μM against the Calu-6 human lung adenocarcinoma line, and 4.8μM against the MCF7 breast tumor cell line, in an MTS cell viability assay. Following treatment with 6b-6d, Calu-6 cells exhibited a significant increase in the mRNA expression for the silenced tumor suppressor genes SFRP2, HCAD and p16, and modest increases in GATA4 message. The compounds described in this paper represent the most potent epigenetic modulators in this series, and have potential for use as antitumor agents.
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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.