ArticleScientific reports2018
Cancer cell responses to Hsp70 inhibitor JG-98: Comparison with Hsp90 inhibitors and finding synergistic drug combinations.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
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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.
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Who cites it
41 citing papers in PubMed, 64 citations in OpenAlex.
- Heat Shock Proteins as Targets for Cancer Therapeutics.Journal of clinical medicine · 2026Review
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- HSPA2 influences the differentiation and production of immunomodulatory mediators in human immortalized epidermal keratinocyte lines.Cell death & disease · 2025Article
- Cancer Cell's Achilles Heels: Considerations for Design of Anti-Cancer Drug Combinations.International journal of molecular sciences · 2024Article
- Review
- Heat Shock Proteins and Breast Cancer.International journal of molecular sciences · 2024Review
- Autocrine regulation of tumor cell repopulation by Hsp70-HMGB1 alarmin complex.Journal of experimental & clinical cancer research : CR · 2023Article
- Article
- Evolution of Resistance to Irinotecan in Cancer Cells Involves Generation of Topoisomerase-Guided Mutations in Non-Coding Genome That Reduce the Chances of DNA Breaks.International journal of molecular sciences · 2023Article
- Heat shock proteins and cancer: The FoxM1 connection.Biochemical pharmacology · 2023Review
- Synthetic Small Molecule Modulators of Hsp70 and Hsp40 Chaperones as Promising Anticancer Agents.International journal of molecular sciences · 2023Review
- Using a Modified Proximity Ligation Protocol to Study the Interaction Between Chaperones and Associated Proteins.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Targeting Triple Negative Breast Cancer Stem Cells by Heat Shock Protein 70 Inhibitors.Cancers · 2022Article
- Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities.MedComm · 2022Review
- Hsp70-Bag3 Module Regulates Macrophage Motility and Tumor Infiltration via Transcription Factor LITAF and CSF1.Cancers · 2022Article
- Protein Quality Control in Glioblastoma: A Review of the Current Literature with New Perspectives on Therapeutic Targets.International journal of molecular sciences · 2022Review
- Allosteric HSP70 inhibitors perturb mitochondrial proteostasis and overcome proteasome inhibitor resistance in multiple myeloma.Cell chemical biology · 2022Article
- Single-cell analysis of human basal cell carcinoma reveals novel regulators of tumor growth and the tumor microenvironment.Science advances · 2022Article
- Cytoplasmic proteotoxicity regulates HRI-dependent phosphorylation of eIF2α via the Hsp70-Bag3 module.iScience · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Hsp70 is a promising anti-cancer target. Our JG-98 series of Hsp70 inhibitors show anti-cancer activities affecting both cancer cells and tumor-associated macrophages. They disrupt Hsp70 interaction with a co-chaperone Bag3 and affect signaling pathways important for cancer development. Due to a prior report that depletion of Hsp70 causes similar responses as depletion of Hsp90, interest to Hsp70 inhibitors as drug prototypes is hampered by potential similarity of their effects to effects of Hsp90 inhibitors. Here, using the Connectivity Map platform we demonstrate that physiological effects of JG-98 are dissimilar from effects of Hsp90 inhibitors, thus justifying development of these compounds. Using gene expression and ActivSignal IPAD platform, we identified pathways modulated by JG-98. Some of these pathways were affected by JG-98 in Bag3-dependent (e.g. ERK) and some in Bag3-independent manner (e.g. Akt or c-myc), indicating multiple effects of Hsp70 inhibition. Further, we identified genes that modulate cellular responses to JG-98, developed approaches to predict potent combinations of JG-98 with known drugs, and demonstrated that inhibitors of proteasome, RNApol, Akt and RTK synergize with JG-98. Overall, here we established unique effects of novel Hsp70 inhibitors on cancer cell physiology, and predicted potential drug combinations for pre-clinical development.
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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.