ArticleScientific reports2017
Anti-leukemia activity of a Hsp70 inhibitor and its hybrid molecules.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 22 citations in OpenAlex.
- Impact of Esomeprazole, Ciprofloxacin and Their Combination on Cervical Cancer Cell Line Proliferation: A Focus on Heat Shock Protein 70 Modulation.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- HSP70 Family in Cancer: Signaling Mechanisms and Therapeutic Advances.Biomolecules · 2023Review
- Synthetic Small Molecule Modulators of Hsp70 and Hsp40 Chaperones as Promising Anticancer Agents.International journal of molecular sciences · 2023Review
- Azaphilones produced by Penicillium maximae with their cell death-inducing activity on Adriamycin-treated cancer cell.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2023Article
- Targeting UPR signaling pathway by dasatinib as a promising therapeutic approach in chronic myeloid leukemia.Medical oncology (Northwood, London, England) · 2022Article
- Heat Shock Protein Member 8 (HSPA8) Is Involved in Porcine Reproductive and Respiratory Syndrome Virus Attachment and Internalization.Microbiology spectrum · 2022Article
- Advances in the study of HSP70 inhibitors to enhance the sensitivity of tumor cells to radiotherapy.Frontiers in cell and developmental biology · 2022Review
- HSP70 and their co-chaperones in the human malaria parasiteFrontiers in molecular biosciences · 2022Review
- Repurposing drugs to target the malaria parasite unfolding protein response.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study we examined the anti-leukemia activity of a small molecule inhibitor of Hsp70 proteins, apoptozole (Az), and hybrids in which it is linked to an inhibitor of either Hsp90 (geldanamycin) or Abl kinase (imatinib). The results of NMR studies revealed that Az associates with an ATPase domain of Hsc70 and thus blocks ATP binding to the protein. Observations made in the cell study indicated that Az treatment promotes leukemia cell death by activating caspase-dependent apoptosis without affecting the caspase-independent apoptotic pathway. Importantly, the hybrids composed of Az and geldanamycin, which have high inhibitory activities towards both Hsp70 and Hsp90, exhibit enhanced anti-leukemia activity relative to the individual inhibitors. However, the Az and imatinib hybrids have weak inhibitory activities towards Hsp70 and Abl, and display lower cytotoxicity against leukemia cells compared to those of the individual constituents. The results of a mechanistic study showed that the active hybrid molecules promote leukemia cell death through a caspase-dependent apoptotic pathway. Taken together, the findings suggest that Hsp70 inhibitors as well as their hybrids can serve as potential anti-leukemia agents.
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