ArticleExperimental & molecular medicine2020
Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1.
Article in Experimental & molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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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
59 citing papers in PubMed, 143 citations in OpenAlex.
- Crosstalk Between the NRF2 Signaling Pathway and Heat Shock Proteins: Implications for Cellular Stress Response and Disease Therapy.Oxidative medicine and cellular longevity · 2026Review
- TRAP1 and its therapeutic potential.Bioorganic & medicinal chemistry letters · 2025Review
- Design of multi-target peptide modulators for protein chaperone networks.Structure (London, England : 1993) · 2025Article
- Targeting proteostasis pathways for cancer therapy.Journal of pharmaceutical analysis · 2025Review
- Exploring the Interplay Between Hyperthermia and Cytotoxic Drugs in Ocular Melanoma Cell Lines: Implications and Variability in Treatment Efficiency.Investigative ophthalmology & visual science · 2025Article
- Combination Strategies with HSP90 Inhibitors in Cancer Therapy: Mechanisms, Challenges, and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A Convergent Approach to Resorcinolic Macrolides to Expand Structural Diversity.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Synthesis, Anticancer Screening, and In Silico Evaluations of Thieno[2,3-Pharmaceuticals (Basel, Switzerland) · 2025Article
- Mitochondrial involvement in PC: improving therapeutic strategies.Frontiers in pharmacology · 2025Review
- Uncovering the Mechanism of Action of Antiprotozoal Agents: A Survey on Photoaffinity Labeling Strategy.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Hiding in plain sight: Optimizing topoisomerase IIα inhibitors into Hsp90β selective binders.European journal of medicinal chemistry · 2024Article
- The Role of eHsp90 in Extracellular Matrix Remodeling, Tumor Invasiveness, and Metastasis.Cancers · 2024Review
- Double-Edged Sword: Exploring the Mitochondria-Complement Bidirectional Connection in Cellular Response and Disease.Biology · 2024Review
- Chaperones-A New Class of Potential Therapeutic Targets in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Identification of HSP90B1 in pan-cancer hallmarks to aid development of a potential therapeutic target.Molecular cancer · 2024Article
- Eternal Youth: A Comprehensive Exploration of Gene, Cellular, and Pharmacological Anti-Aging Strategies.International journal of molecular sciences · 2024Review
- Prognosis and therapeutic significance of IGF-1R-related signaling pathway gene signature in glioma.Frontiers in cell and developmental biology · 2024Article
- Targeting the Mitochondrial Chaperone TRAP1 Alleviates Vascular Pathologies in Ischemic Retinopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Elucidation of novel TRAP1-Selective inhibitors that regulate mitochondrial processes.European journal of medicinal chemistry · 2023Article
- Exploration of anti-leukemic effect of soft coral-derived 13-acetoxysarcocrassolide: Induction of apoptosis via oxidative stress as a potent inhibitor of heat shock protein 90 and topoisomerase II.The Kaohsiung journal of medical sciences · 2023Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity.
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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.