ArticleJournal of medicinal chemistry2018
Discovery of the First-in-Class Dual Histone Deacetylase-Proteasome Inhibitor.
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 28 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
28 citing papers in PubMed, 76 citations in OpenAlex.
- H1-0 is a specific mediator of the repressive ETV6::RUNX1 transcriptional landscape in preleukemia and B cell acute lymphoblastic leukemia.HemaSphere · 2025Article
- PARP9 drives the malignant progression of pancreatic cancer cells by regulating apoptosis, DNA damage, and multidrug efflux systems.Frontiers in cell and developmental biology · 2025Article
- The enhancing effects of selenomethionine on harmine in attenuating pathological cardiac hypertrophy via glycolysis metabolism.Journal of cellular and molecular medicine · 2024Article
- Development of Epigenetic Modifiers with Therapeutic Potential in FMS-Related Tyrosine Kinase 3/Internal Tandem Duplication (FLT3/ITD) Acute Myeloid Leukemia and Other Blood Malignancies.ACS pharmacology & translational science · 2024Article
- Histone deacetylase (HDAC) inhibitor specificity determinants are preserved in a class of dual HDAC/non-covalent proteasome inhibitors.Bioorganic & medicinal chemistry · 2024Article
- Development of First-in-Class Dual Sirt2/HDAC6 Inhibitors as Molecular Tools for Dual Inhibition of Tubulin Deacetylation.Journal of medicinal chemistry · 2023Article
- Difluoromethyl-1,3,4-oxadiazoles Are Selective, Mechanism-Based, and Essentially Irreversible Inhibitors of Histone DeacetylaseJournal of medicinal chemistry · 2023Article
- Entinostat-Bortezomib Hybrids against Multiple Myeloma.Molecules (Basel, Switzerland) · 2023Article
- Solid-Phase Parallel Synthesis of Dual Histone Deacetylase-Cyclooxygenase Inhibitors.Molecules (Basel, Switzerland) · 2023Article
- Development of Fluorinated Peptoid-Based Histone Deacetylase (HDAC) Inhibitors for Therapy-Resistant Acute Leukemia.Journal of medicinal chemistry · 2022Article
- Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance.Molecules (Basel, Switzerland) · 2022Review
- A first-in-class anticancer dual HDAC2/FAK inhibitors bearing hydroxamates/benzamides capped by pyridinyl-1,2,4-triazoles.European journal of medicinal chemistry · 2021Article
- Exploring EZH2-Proteasome Dual-Targeting Drug Discovery through a Computational Strategy to Fight Multiple Myeloma.Molecules (Basel, Switzerland) · 2021Article
- Shifting the paradigm in treating multi-factorial diseases: polypharmacological co-inhibitors of HDAC6.RSC medicinal chemistry · 2021Review
- Article
- Spiroindoline-Capped Selective HDAC6 Inhibitors: Design, Synthesis, Structural Analysis, and Biological Evaluation.ACS medicinal chemistry letters · 2020Article
- Multicomponent Synthesis, Binding Mode, and Structure-Activity Relationship of Selective Histone Deacetylase 6 (HDAC6) Inhibitors with Bifurcated Capping Groups.Journal of medicinal chemistry · 2020Article
- Binding of inhibitors to active-site mutants of CD1, the enigmatic catalytic domain of histone deacetylase 6.Acta crystallographica. Section F, Structural biology communications · 2020Article
- Design, synthesis and pharmacological evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152): a novel triple angiokinase inhibitor for cancer therapy.Acta pharmaceutica Sinica. B · 2020Article
- Design and Synthesis of Dihydroxamic Acids as HDAC6/8/10 Inhibitors.ChemMedChem · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Dual- or multitarget drugs have emerged as a promising alternative to combination therapies. Proteasome inhibitors (PIs) possess synergistic activity with histone deacetylase (HDAC) inhibitors due to the simultaneous blockage of the ubiquitin degradation and aggresome pathways. Here, we present the design, synthesis, binding modes, and anticancer properties of RTS-V5 as the first-in-class dual HDAC-proteasome ligand. The inhibition of both targets was confirmed by biochemical and cellular assays as well as X-ray crystal structures of the 20S proteasome and HDAC6 complexed with RTS-V5. Cytotoxicity assays with leukemia and multiple myeloma cell lines as well as therapy refractory primary patient-derived leukemia cells demonstrated that RTS-V5 possesses potent and selective anticancer activity. Our results will thus guide the structure-based optimization of dual HDAC-proteasome inhibitors for the treatment of hematological malignancies.
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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.