ArticleCancer research2013
Tasquinimod Is an Allosteric Modulator of HDAC4 survival signaling within the compromised cancer microenvironment.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Efficacy of tasquinimod in men with metastatic castration-resistant prostate cancer: A meta-analysis of randomized controlled trials.Medicine · 2018Pooled it
- Long-term survival and biomarker correlates of tasquinimod efficacy in a multicenter randomized study of men with minimally symptomatic metastatic castration-resistant prostate cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Trial
- Proteogenomic Analysis of HDAC4 and HDAC5 in Uveal Melanoma.Molecular medicine (Cambridge, Mass.) · 2026Article
- Review
- HDAC4 regulates hASC osteogenesis and bone regeneration by mediating SMAD4 via histone acetylation.Stem cell reports · 2026Article
- Neutrophil-derived S100A8/A9 impairs megakaryocyte maturation in immune thrombocytopenia.Nature communications · 2026Article
- Mapping Functionally Relevant Tractable Lysines of Challenging Protein Targets by Covalent Fragment Screening.Chembiochem : a European journal of chemical biology · 2026Article
- An HDAC4-specific PROTAC degrader achieves radiation sensitization by enhancing ferroptosis in lung cancer.Nature communications · 2026Article
- Preclinical efficacy of tasquinimod in myelodysplastic neoplasms: Restoring erythropoiesis and mitigating bone loss.HemaSphere · 2026Article
- S100A9 as a shared biomarker and mediator of metabolic dysfunction in peripheral artery disease and sarcopenia.Frontiers in genetics · 2026Article
- Comparative Investigation of Cytotoxic Effects of Structurally Diverse Small Molecules and In Silico Analysis of 1-Acetyl-4-(4-Hydroxyphenyl)piperazine.Journal of cellular and molecular medicine · 2026Article
- Targeting S100A8/A9: a molecular gateway to oral inflammation, microglial activation and neuroinflammation.Frontiers in immunology · 2026Review
- Targeting S100A9-mediated inflammation: a novel therapeutic approach for CLL.Blood advances · 2025Review
- Quinoline Quest: Kynurenic Acid Strategies for Next-Generation Therapeutics via Rational Drug Design.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Review
- Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Acquired resistance to molecularly targeted therapies for cancer.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Characterization of structural, biochemical, pharmacokinetic, and pharmacodynamic properties of the LSD1 inhibitor bomedemstat in preclinical models.The Prostate · 2024Article
- Zinc-Dependent Histone Deacetylases in Lung Endothelial Pathobiology.Biomolecules · 2024Review
- Acetylation and Phosphorylation in the Regulation of Hypoxia-Inducible Factor Activities: Additional Options to Modulate Adaptations to Changes in Oxygen Levels.Life (Basel, Switzerland) · 2023Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Tasquinimod is an orally active antiangiogenic drug that is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer. However, the target of this drug has remained unclear. In this study, we applied diverse strategies to identify the histone deacetylase HDAC4 as a target for the antiangiogenic activity of tasquinimod. Our comprehensive analysis revealed allosteric binding (Kd 10-30 nmol/L) to the regulatory Zn(2+) binding domain of HDAC4 that locks the protein in a conformation preventing HDAC4/N-CoR/HDAC3 complex formation. This binding inhibited colocalization of N-CoR/HDAC3, thereby inhibiting deacetylation of histones and HDAC4 client transcription factors, such as HIF-1α, which are bound at promoter/enhancers where epigenetic reprogramming is required for cancer cell survival and angiogenic response. Through this mechanism, tasquinimod is effective as a monotherapeutic agent against human prostate, breast, bladder, and colon tumor xenografts, where its efficacy could be further enhanced in combination with a targeted thapsigargin prodrug (G202) that selectively kills tumor endothelial cells. Together, our findings define a mechanism of action of tasquinimod and offer a perspective on how its clinical activity might be leveraged in combination with other drugs that target the tumor microenvironment. Cancer Res; 73(4); 1386-99. ©2012 AACR.
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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.