ArticleJournal of the American Chemical Society2012
Development of a Grp94 inhibitor.
Article in Journal of the American Chemical Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 113 citations in OpenAlex.
- Guaianolide dimer KGA-1002 targets GRP94 and triggers unfolded protein response-associated degradation of SKP2/AKT axis as a novel antihepatoma agent.Journal of advanced research · 2026Article
- Design, synthesis, and biological properties exhibited by 1,2,3-triazole based Grp94-selective inhibitors.European journal of medicinal chemistry · 2026Article
- Large-scale single-cell analysis and in silico perturbation reveal dynamic evolution of HCC: from initiation to therapeutic targeting.NPJ precision oncology · 2026Article
- A Novel Small-Molecule GRP94 Modulator Increases PCSK9 Secretion and Promotes LDLR Degradation.Life (Basel, Switzerland) · 2025Article
- Glucose-regulated protein 94 (Grp94/gp96) in viral pathogenesis: Insights into its role and therapeutic potentials.European journal of medicinal chemistry · 2025Review
- The structural and functional dynamics of BiP and Grp94: opportunities for therapeutic discovery.Trends in pharmacological sciences · 2025Review
- Conformationally Restricted Grp94-Selective Inhibitors.ACS omega · 2025Article
- N-Glycosylation-Induced Pathologic Protein Conformations as a Tool to Guide the Selection of Biologically Active Small Molecules.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- Inhibiting spinal cord-specific hsp90 isoforms reveals a novel strategy to improve the therapeutic index of opioid treatment.Scientific reports · 2024Article
- How aberrant N-glycosylation can alter protein functionality and ligand binding: An atomistic view.Structure (London, England : 1993) · 2023Article
- Pan-HSP90 ligand binding reveals isoform-specific differences in plasticity and water networks.Protein science : a publication of the Protein Society · 2023Article
- HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review).Oncology reports · 2023Review
- Pharmacological targeting of endoplasmic reticulum stress in disease.Nature reviews. Drug discovery · 2022Review
- Endoplasmic Reticulum Stress of Gut Enterocyte and Intestinal Diseases.Frontiers in molecular biosciences · 2022Review
- Hsp90β inhibition upregulates interferon response and enhances immune checkpoint blockade therapy in murine tumors.Frontiers in immunology · 2022Article
- Inhibitors of theCells · 2021Review
- Structure-Based Design, Synthesis, and Biological Evaluation of Hsp90β-Selective Inhibitors.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- FBXL2 counteracts Grp94 to destabilize EGFR and inhibit EGFR-driven NSCLC growth.Nature communications · 2021Article
- Selective Inhibition of the Hsp90α Isoform.Angewandte Chemie (International ed. in English) · 2021Article
- The Development of Hsp90β-Selective Inhibitors to Overcome Detriments Associated withJournal of medicinal chemistry · 2021Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Heat shock protein 90 (Hsp90) represents a promising therapeutic target for the treatment of cancer and other diseases. Unfortunately, results from clinical trials have been disappointing as off-target effects and toxicities have been observed. These detriments may be a consequence of pan-Hsp90 inhibition, as all clinically evaluated Hsp90 inhibitors simultaneously disrupt all four human Hsp90 isoforms. Using a structure-based approach, we designed an inhibitor of Grp94, the ER-resident Hsp90. The effect manifested by compound 2 on several Grp94 and Hsp90α/β (cytosolic isoforms) clients were investigated. Compound 2 prevented intracellular trafficking of the Toll receptor, inhibited the secretion of IGF-II, affected the conformation of Grp94, and suppressed Drosophila larval growth, all Grp94-dependent processes. In contrast, compound 2 had no effect on cell viability or cytosolic Hsp90α/β client proteins at similar concentrations. The design, synthesis, and evaluation of 2 are described herein.
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What OpenQuestion holds
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.