ArticleMolecular pharmacology2015
KU675, a Concomitant Heat-Shock Protein Inhibitor of Hsp90 and Hsc70 that Manifests Isoform Selectivity for Hsp90α in Prostate Cancer Cells.
Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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
26 citing papers in PubMed, 39 citations in OpenAlex.
- A Phase II Study of Ganetespib as Second-line or Third-line Therapy for Metastatic Pancreatic Cancer.American journal of clinical oncology · 2018Trial
- Optimization of an Hsp90β-selective inhibitor via exploration of the Hsp90 N-terminal ATP-binding pocket.European journal of medicinal chemistry · 2025Article
- The Hsp90β Isoform: An Attractive Target for Drug Development.Medicinal research reviews · 2025Review
- The possibilities and challenges associated with selective targetingTransactions of the Royal Society of South Africa. Royal Society of South Africa · 2025Article
- Hiding in plain sight: Optimizing topoisomerase IIα inhibitors into Hsp90β selective binders.European journal of medicinal chemistry · 2024Article
- Development of Hsp90 C-terminal inhibitors with noviomimetics that manifest anti-proliferative activities.RSC medicinal chemistry · 2024Article
- Versatile Design of Organic Polymeric Nanoparticles for Photodynamic Therapy of Prostate Cancer.ACS materials Au · 2024Review
- Recent advances toward the development of Hsp90 C-terminal inhibitors.Bioorganic & medicinal chemistry letters · 2023Review
- Cytosolic Hsp90 Isoform-Specific Functions and Clinical Significance.Biomolecules · 2022Review
- Hsp90β inhibition upregulates interferon response and enhances immune checkpoint blockade therapy in murine tumors.Frontiers in immunology · 2022Article
- Selective Inhibition of the Hsp90α Isoform.Angewandte Chemie (International ed. in English) · 2021Article
- The Development of Hsp90β-Selective Inhibitors to Overcome Detriments Associated withJournal of medicinal chemistry · 2021Article
- Clinical Implications ofInternational journal of medical sciences · 2021Observational
- Article
- A Long Non-coding RNA Lnc712 Regulates Breast Cancer Cell Proliferation.International journal of biological sciences · 2020Article
- Identification of Isoform-Selective Ligands for the Middle Domain of Heat Shock Protein 90 (Hsp90).International journal of molecular sciences · 2019Article
- Hsc70 Interacts with β4GalT5 to Regulate the Growth of Gliomas.Neuromolecular medicine · 2019Article
- The Alpha Isoform of Heat Shock Protein 90 and the Co-chaperones p23 and Cdc37 Promote Opioid Anti-nociception in the Brain.Frontiers in molecular neuroscience · 2019Article
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Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The 90-kDa heat-shock protein (Hsp90) assists in the proper folding of numerous mutated or overexpressed signal transduction proteins that are involved in cancer. Inhibiting Hsp90 consequently is an attractive strategy for cancer therapy as the concomitant degradation of multiple oncoproteins may lead to effective antineoplastic agents. Here we report a novel C-terminal Hsp90 inhibitor, designated KU675, that exhibits potent antiproliferative and cytotoxic activity along with client protein degradation without induction of the heat-shock response in both androgen-dependent and -independent prostate cancer cell lines. In addition, KU675 demonstrates direct inhibition of Hsp90 complexes as measured by the inhibition of luciferase refolding in prostate cancer cells. In direct binding studies, the internal fluorescence signal of KU675 was used to determine the binding affinity of KU675 to recombinant Hsp90α, Hsp90β, and Hsc70 proteins. The binding affinity (Kd) for Hsp90α was determined to be 191 μM, whereas the Kd for Hsp90β was 726 μM, demonstrating a preference for Hsp90α. Western blot experiments with four different prostate cancer cell lines treated with KU675 supported this selectivity by inducing the degradation of Hsp90α -: dependent client proteins. KU675 also displayed binding to Hsc70 with a Kd value at 76.3 μM, which was supported in cellular by lower levels of Hsc70-specific client proteins on Western blot analyses. Overall, these findings suggest that KU675 is an Hsp90 C-terminal inhibitor, as well as a dual inhibitor of Hsc70, and may have potential use for the treatment of cancer.
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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.