PU-H71 (NSC 750424): a molecular masterpiece that targets HSP90 in cancer and beyond

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Saber S.; Abdelhady R.; Elhemely M.A.; Elmorsy E.A.; Hamad R.S.; Abdel-Reheim M.A.; El-kott A.F.; AlShehri M.A.; Morsy K.; AlSheri A.S.; Youssef M.E.

Journal: Frontiers in Pharmacology

Publisher: Frontiers Media SA

Publication Date: 5 November 2024

Volume / Issue: Volume 15

Article No.: 1475998

ISSN: 16639812

DOI: 10.3389/fphar.2024.1475998

Scopus: View on Scopus

Document Type: Review

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Saber S., Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Abdelhady R., Pharmacology and Toxicology Department, Faculty of Pharmacy, Fayoum University, Fayoum, Egypt, Pharmacology and Toxicology Department, Faculty of Pharmacy, Egyptian Chinese University, Cairo, Egypt; Elhemely M.A., School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom; Elmorsy E.A., Department of Pharmacology and Therapeutics, College of Medicine, Qassim University, Buraidah, Saudi Arabia, Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Hamad R.S., Biological Sciences Department, College of Science, King Faisal University, Al Ahsa, Saudi Arabia, Central Laboratory, Theodor Bilharz Research Institute, Giza, Egypt; Abdel-Reheim M.A., Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra, Saudi Arabia, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, Egypt; El-kott A.F., Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia, Department of Zoology, Faculty of Science, Damanhour University, Damanhour, Egypt; AlShehri M.A., Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia; Morsy K., Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia, Department of Zoology, Faculty of Science, Cairo University, Cairo, Egypt; AlSheri A.S., Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia; Youssef M.E., Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt

Abstract

Heat shock protein 90 (HSP90) is a pivotal molecular chaperone with multifaceted roles in cellular health and disease. Herein, we explore how HSP90 orchestrates cellular stress responses, particularly through its partnership with heat shock factor 1 (HSF-1). PU-H71, a selective inhibitor of HSP90, demonstrates significant potential in cancer therapy by targeting a wide array of oncogenic pathways. By inducing the degradation of multiple client proteins, PU-H71 disrupts critical signaling pathways such as MAPK, PI3K/Akt, JAK/STAT, EGFR, and mTOR, which are essential for cancer cell survival, proliferation, and metastasis. We examined its impact on combating triple-negative breast cancer and enhancing the effectiveness of carbon-ion beam therapy, offering new avenues for cancer treatment. Furthermore, the dual inhibition of HSP90A and HSP90B1 by PU-H71 proves highly effective in the context of myeloma, providing fresh hope for patients with this challenging malignancy. We delve into its potential to induce apoptosis in B-cell lymphomas that rely on Bcl6 for survival, highlighting its relevance in the realm of hematologic cancers. Shifting our focus to hepatocellular carcinoma, we explore innovative approaches to chemotherapy. Moreover, the current review elucidates the potential capacity of PU-H71 to suppress glial cell activation paving the way for developing novel therapeutic strategies for neuroinflammatory disorders. Additionally, the present report also suggests the promising role of PU-H71 in JAK2-dependent myeloproliferative neoplasms. Eventually, our report sheds more light on the multiple functions of HSP90 protein as well as the potential therapeutic benefit of its selective inhibitor PU-H71 in the context of an array of diseases, laying the foundations for the development of novel therapeutic approaches that could achieve better treatment outcomes. Copyright © 2024 Saber, Abdelhady, Elhemely, Elmorsy, Hamad, Abdel-Reheim, El-kott, AlShehri, Morsy, AlSheri and Youssef.

Keywords

apoptosis; Hsp90; oncogenic signals; PU-H71 (NSC 750424); tumorigenesis; chaperone; epidermal growth factor receptor; heat shock protein 90; heat shock transcription factor 1; mammalian target of rapamycin; zelavespib; B cell lymphoma; carcinogenesis; cell activation; cell survival; cellular stress response; drug therapy; glia cell; human; liver cell carcinoma; metastasis; myeloproliferative neoplasm; neoplastic cell transformation; nervous system inflammation; pharmacology; review; signal transduction; triple negative breast cancer

Citation Information

Scopus Citations: 11

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