Review
Cell Biology
Xiude Ren, Tao Li, Wei Zhang, Xuejun Yang
Summary: Heat-shock protein 90 (HSP90) is an important molecule chaperone associated with tumorigenesis and malignancy. It plays a role in the malignant behaviors of cancer cells, but currently there are no effective single-agent treatments. Combining HSP90 inhibitors with other anticancer therapies may be a better strategy.
Review
Cell Biology
Cheng Chang, Xin Tang, David T. Woodley, Mei Chen, Wei Li
Summary: For a long time, the cytosolic Hsp90 alpha and Hsp90 beta proteins have been considered evolutionarily conserved, ATP-driven chaperones that play a crucial role in basic research and clinical trials. Recent studies have challenged this notion and highlighted the failures of paradigm-based clinical trials. It is now known that Hsp90 alpha and Hsp90 beta are ubiquitously expressed in all cell types but have distinct and irreplaceable functions. Understanding the differences between Hsp90 alpha and Hsp90 beta could lead to new therapeutic approaches for human disorders such as cancer.
Article
Chemistry, Multidisciplinary
Silas Wurnig, Melina Vogt, Julian Hogenkamp, Niklas Dienstbier, Arndt Borkhardt, Sanil Bhatia, Finn K. Hansen
Summary: Despite limitations with HSP90 inhibitors as anticancer drugs, a new approach using PROTACs to degrade the protein shows promise. This study focuses on designing and evaluating geldanamycin-based HSP90 degraders based on the PROTAC technology. The best degrader, 3a, effectively reduced HSP90 alpha and HSP90 beta levels in cells using the ubiquitin-proteasome pathway.
FRONTIERS IN CHEMISTRY
(2023)
Article
Oncology
Zeynep Eroglu, Y. Ann Chen, Inna Smalley, Jiannong Li, Joseph K. Markowitz, Andrew S. Brohl, Leticia Tetteh, Hayley Taylor, Vernon K. Sondak, Nikhil I. Khushalani, Keiran S. M. Smalley
Summary: In this study, the efficacy and safety of vemurafenib and cobimetinib in combination with different doses of the HSP90 inhibitor XL888 for the treatment of advanced melanoma were explored. The study found that this combination therapy showed activity in some patients, but also had significant toxicity.
Article
Chemistry, Medicinal
Sanket J. Mishra, Weiya Liu, Kristin Beebe, Monimoy Banerjee, Caitlin N. Kent, Vitumbiko Munthali, John Koren, John A. Taylor, Leonard M. Neckers, Jeffrey Holzbeierlein, Brian S. J. Blagg
Summary: Hsp90 proteins play a crucial role in cancer progression, and inhibiting their activity may be beneficial for cancer treatment. Current Hsp90 inhibitors target all isoforms, potentially leading to adverse effects. Utilizing Hsp90 beta-selective inhibitors as a new approach for cancer therapy holds promise in reducing side effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Tanya Ju-Ngam, Nichanun McMillan, Mamoru Yoshimizu, Hisae Kasai, Ratree Wongpanya, Prapansak Srisapoome
Summary: This research conducted molecular characterization and biofunctional analyses of Hsp40 and Hsp90 genes in giant river prawns under various stress conditions. The highest similarity scores of these genes were found with crustaceans. Expression patterns of Mr-hsp40 and Mr-hsp90 were different under Aeromonas hydrophila challenge and heat-cold shock conditions, highlighting their significant roles in stress responses.
Article
Cell Biology
Ruben M. L. Colunga Biancatelli, Pavel Solopov, Christiana Dimitropoulou, Betsy Gregory, Tierney Day, John D. Catravas
Summary: The HSP90 inhibitor, AT13387, shows promising potential in preventing chronic lung injury induced by HCl and protecting the endothelial barrier. It reduces inflammation and fibrosis caused by HCl exposure and restores lung function.
Review
Cell Biology
Melissa Louise Stofberg, Celine Caillet, Marianne de Villiers, Tawanda Zininga
Summary: Malaria remains a major killer parasitic disease in tropical settings, with the development of antimalarial drug resistance posing a significant challenge in disease control. Therefore, there is a need to explore new strategies and treatment options to reverse the development of antimalarial drug resistance.
Article
Biochemistry & Molecular Biology
Roberto Leon, Jorge Soto-Delgado, Elizabeth Montero, Matias Vargas
Summary: The study utilizes a fragment-based drug design strategy and heuristic search algorithm to design new inhibitors by deconstructing known ligands and reassembling fragments to generate new ligands. Evaluation of the approaches involves comparing the binding energy of the new ligands with the known ligands.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Hui Yi Liew, Xin Yoong Tan, Hong Hao Chan, Kooi Yeong Khaw, Yong Sze Ong
Summary: This review analyzes the chemical and biological activities of natural Hsp90 inhibitors, discusses their efficacy in tumor models, and explores their pharmacodynamics and pharmacokinetics.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Stefan Tukaj, Krzysztof Sitko
Summary: Over a hundred different autoimmune diseases have been described to date, affecting various organs including the skin. The loss of immune tolerance in autoimmune diseases leads to chronic inflammation and tissue damage. Current treatments focus on immunosuppression but may cause serious adverse effects. Heat shock proteins Hsp90 and Hsp70 have been identified as potential therapeutic targets for autoimmune skin diseases.
Article
Veterinary Sciences
Samuel A. Atkin, Abu Saleh Md Moin, Stephen L. Atkin, Alexandra E. Butler
Summary: This study investigated the effects of hypoglycemia on the heat shock-related protein pathway. The results showed that hypoglycemia significantly decreased the expression of HSP90, 70, 27, and ubiquitin proteins, which are important for the protective response against heat stress.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Ziva Zajec, Jaka Dernovsek, Martina Gobec, Tihomir Tomasic
Summary: Hsp90 is a promising target for cancer treatment. The discovery of a novel class of Hsp90 CTD inhibitors through virtual screening provides new starting points for further development, showing enhanced antiproliferative activities in breast cancer and sarcoma cell lines.
Article
Multidisciplinary Sciences
Sayan Dutta Gupta, Dae-Geun Song, SueJung Lee, Jae Wook Lee, Jin-Soo Park, Chrisostomos Prodromou, Cheol-Ho Pan
Summary: Hsp90 is a potential anticancer target due to its chaperoning effect on oncogenic proteins. Its activity relies on the hydrolysis of ATP to ADP and phosphate. Inhibiting the binding of ATP to Hsp90 effectively suppresses its function.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Chemistry, Medicinal
Andrew J. Ambrose, Jared Sivinski, Christopher J. Zerio, Xiaoyi Zhu, Jack Godek, Vlad K. Kumirov, Teresa Coma Brujas, Joan Torra Garcia, Anandhan Annadurai, Cody J. Schmidlin, Alyssa Werner, Taoda Shi, Reza Beheshti Zavareh, Luke Lairson, Donna D. Zhang, Eli Chapman
Summary: A recent study found that a fluorescence polarization assay can identify substrate-competitive Hsp70 inhibitors with isoform selectivity. In this study, the assay was used in a moderate-throughput screen to discover a druglike amino-acid-based inhibitor that specifically targets the endoplasmic reticular Hsp70, Grp78. The potency and selectivity of the inhibitor were further optimized through structure-activity relationship studies, but it showed little effect on cancer cell lines until it was combined with endoplasmic reticulum stress-inducing agents. The inhibitor demonstrated better potency in a spheroid tumor model compared to two-dimensional models. These findings represent the first reported isoform-selective small-molecule-competitive inhibitors of an Hsp70-substrate interaction.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Sreedhar Reddy Tummalapalli, Rohit Bhat, Craig Waitt, Henk Eshuis, David P. Rotella
TETRAHEDRON LETTERS
(2017)
Article
Multidisciplinary Sciences
Andrew M. Tobias, Dea Toska, Keith Lange, Tyler Eck, Rohit Bhat, Cheryl A. Janson, David P. Rotella, Ueli Gubler, Nina M. Goodey
Article
Chemistry, Medicinal
Sreedhar R. Tummalapalli, Rohit Bhat, Agnieszka Chojnowski, Monika Prorok, Tamara Kreissir, Ronald Goldberg, Stacie Canan, Natalie Hawryluk, Deborah Mortensen, Vikram Khetan, Jerome Zeldis, John J. Siekierka, David P. Rotella
ACS MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Chemistry, Medicinal
Rohit Bhat, James A. Fishback, Rae R. Matsumoto, Jacques H. Poupaert, Christopher R. McCurdy
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2013)
Article
Chemistry, Medicinal
Rohit Bhat, Amna T. Adam, Jungeun Jasmine Lee, Gaspard Deloison, Yves Rouille, Karin Seron, David P. Rotella
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2014)
Article
Chemistry, Medicinal
Daniel J. Buzard, Sun Hee Kim, Juerg Lehmann, Sangdon Han, Imelda Calderon, Amy Wong, Andrew Kawasaki, Sanju Narayanan, Rohit Bhat, Tawfik Gharbaoui, Luis Lopez, Dawei Yue, Kevin Whelan, Hussien Al-Shamma, David J. Unett, Hsin-Hui Shu, Shiu-Feng Tung, Steve Chang, Ching-Fen Chuang, Michael Morgan, Abu Sadeque, Zhi-Liang Chu, James N. Leonard, Robert M. Jones
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2014)
Article
Chemistry, Medicinal
Rohit Bhat, Amna T. Adam, Jungeun Jasmine Lee, Thomas A. Gasiewicz, Ellen C. Henry, David P. Rotella
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2014)
Review
Chemistry, Medicinal
Sanju Narayanan, Rohit Bhat, Christophe Mesangeau, Jacques H. Poupaert, Christopher R. McCurdy
FUTURE MEDICINAL CHEMISTRY
(2011)
Article
Chemistry, Analytical
James A. Fishback, Abagail Rosen, Rohit Bhat, Christopher R. McCurdy, Rae R. Matsumoto
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2012)
Article
Medicine, General & Internal
Suvarna Patil, Netaji Patil, Charudatta Joglekar, Arvind Yadav, Anup Nilawar, Ulka Banavali, Rohit Bhat, Vijay Dombale, Bhushan Warpe, Rachana Mohite, Kiran Joshi