ArticleNature chemistry2013
Synthesis of 19-substituted geldanamycins with altered conformations and their binding to heat shock protein Hsp90.
Article in Nature chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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Who cites it
32 citing papers in PubMed, 84 citations in OpenAlex.
- Synthesis and Applications of Sulfur-Containing Macrocycles.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Review
- Reblastatin as a neuroprotective agent in temporal lobe epilepsy and excitotoxic conditions of Alzheimer's disease and Parkinson's disease.Acta pharmaceutica Sinica. B · 2026Article
- Geldanamycin, a Naturally Occurring Inhibitor of Hsp90 and a Lead Compound for Medicinal Chemistry.Journal of medicinal chemistry · 2024Review
- Geldanamycins: Potent Hsp90 Inhibitors with Significant Potential in Cancer Therapy.International journal of molecular sciences · 2024Review
- Quinones as Neuroprotective Agents.Antioxidants (Basel, Switzerland) · 2023Review
- Cascade Transformation of the Ansamycin Benzoquinone Core into Benzoxazole Influencing Anticancer Activity and Selectivity.The Journal of organic chemistry · 2023Article
- Review
- The KEAP1-NRF2 System and Esophageal Cancer.Cancers · 2022Review
- Nigericin and Geldanamycin Are Phytotoxic Specialized Metabolites Produced by the Plant PathogenMicrobiology spectrum · 2022Article
- Microarray-Based Screening of Putative HSP90 Inhibitors Predicted and Isolated from Microorganisms.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Design and synthesis of isothiocyanate-containing hybrid androgen receptor (AR) antagonist to downregulate AR and induce ferroptosis in GSH-Deficient prostate cancer cells.Chemical biology & drug design · 2021Article
- NRF2 and the Ambiguous Consequences of Its Activation during Initiation and the Subsequent Stages of Tumourigenesis.Cancers · 2020Review
- Synthesis and biological evaluation of geldanamycin-ferulic acid conjugate as a potent Hsp90 inhibitor.RSC advances · 2019Article
- Regulation of Geldanamycin Biosynthesis by Cluster-Situated Transcription Factors and the Master Regulator PhoP.Antibiotics (Basel, Switzerland) · 2019Review
- Chaperome heterogeneity and its implications for cancer study and treatment.The Journal of biological chemistry · 2019Review
- Article
- Mccrearamycins A-D, Geldanamycin-Derived Cyclopentenone Macrolactams from an Eastern Kentucky Abandoned Coal Mine Microbe.Angewandte Chemie (International ed. in English) · 2017Article
- A Novel Hsp90 Inhibitor Activates Compensatory Heat Shock Protein Responses and Autophagy and Alleviates Mutant A53T α-Synuclein Toxicity.Molecular pharmacology · 2015Article
- Sensitization of multidrug-resistant human cancer cells to Hsp90 inhibitors by down-regulation of SIRT1.Oncotarget · 2015Article
- Computational predictions of corroles as a class of Hsp90 inhibitors.Molecular bioSystems · 2015Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
The benzoquinone ansamycin geldanamycin and its derivatives are inhibitors of heat shock protein Hsp90, an emerging target for novel therapeutic agents both in cancer and in neurodegeneration. However, the toxicity of these compounds to normal cells has been ascribed to reaction with thiol nucleophiles at the quinone 19-position. We reasoned that blocking this position would ameliorate toxicity, and that it might also enforce a favourable conformational switch of the trans-amide group into the cis-form required for protein binding. Here, we report an efficient synthesis of such 19-substituted compounds and realization of our hypotheses. Protein crystallography established that the new compounds bind to Hsp90 with, as expected, a cis-amide conformation. Studies on Hsp90 inhibition in cells demonstrated the molecular signature of Hsp90 inhibitors: decreases in client proteins with compensatory increases in other heat shock proteins in both human breast cancer and dopaminergic neural cells, demonstrating their potential for use in the therapy of cancer or neurodegenerative diseases.
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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.