ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Experimental Anti-Inflammatory Drug Semapimod Inhibits TLR Signaling by Targeting the TLR Chaperone gp96.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Recent progress in anti-Chikungunya virus drug discovery: Focus on the viral life cycle and direct-acting antivirals.Virologica Sinica · 2026Review
- A quantitative high-throughput screening pipeline to identify small molecule inhibitors of Chikungunya nsP2 protease.Scientific reports · 2025Article
- Discovery and optimization of a guanylhydrazone-based small molecule to replace bFGF for cell culture applications.Biochemistry and biophysics reports · 2025Article
- The structural and functional dynamics of BiP and Grp94: opportunities for therapeutic discovery.Trends in pharmacological sciences · 2025Review
- Rapid Natural Killer Cell Gene Responses, Generated by TLR Ligand-Induced Trained Immunity, Provide Protection to Bacterial Infection inInternational journal of molecular sciences · 2025Article
- High-Throughput Screening of More Than 30,000 Compounds for Anthelmintics against Gastrointestinal Nematode Parasites.ACS infectious diseases · 2025Article
- Discovery of antibiotics that selectively kill metabolically dormant bacteria.Cell chemical biology · 2024Article
- High-Throughput Screening of the Repurposing Hub Library to Identify Drugs with Novel Inhibitory Activity againstJournal of fungi (Basel, Switzerland) · 2023Article
- The biology and inhibition of glucose-regulated protein 94/gp96.Medicinal research reviews · 2022Review
- Hypoxia Tolerant Species: The Wisdom of Nature Translated into Targets for Stroke Therapy.International journal of molecular sciences · 2021Review
- Inhibition of heat shock protein 90 alleviates cholestatic liver injury by decreasing IL-1β and IL-18 expression.Experimental and therapeutic medicine · 2021Article
- Ligustrazine Alleviate Acute Lung Injury Through Suppressing Pyroptosis and Apoptosis of Alveolar Macrophages.Frontiers in pharmacology · 2021Article
- Regulation of dendritic cell function improves survival in experimental sepsis through immune chaperone.Innate immunity · 2019Article
- Juniperonic Acid Incorporation into the Phospholipids of Murine Macrophage Cells Modulates Pro-Inflammatory Mediator Production.Inflammation · 2018Article
- Retention of normal glia function by an isoform-selective protein kinase inhibitor drug candidate that modulates cytokine production and cognitive outcomes.Journal of neuroinflammation · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Semapimod, a tetravalent guanylhydrazone, suppresses inflammatory cytokine production and has potential in a variety of inflammatory and autoimmune disorders. The mechanism of action of Semapimod is not well understood. In this study, we demonstrate that in rat IEC-6 intestinal epithelioid cells, Semapimod inhibits activation of p38 MAPK and NF-κB and induction of cyclooxygenase-2 by TLR ligands, but not by IL-1β or stresses. Semapimod inhibits TLR4 signaling (IC50 ≈0.3 μmol) and acts by desensitizing cells to LPS; it fails to block responses to LPS concentrations of ≥5 μg/ml. Inhibition of TLR signaling by Semapimod is almost instantaneous: the drug is effective when applied simultaneously with LPS. Semapimod blocks cell-surface recruitment of the MyD88 adapter, one of the earliest events in TLR signaling. gp96, the endoplasmic reticulum-localized chaperone of the HSP90 family critically involved in the biogenesis of TLRs, was identified as a target of Semapimod using ATP-desthiobiotin pulldown and mass spectroscopy. Semapimod inhibits ATP-binding and ATPase activities of gp96 in vitro (IC50 ≈0.2-0.4 μmol). On prolonged exposure, Semapimod causes accumulation of TLR4 and TLR9 in perinuclear space, consistent with endoplasmic reticulum retention, an anticipated consequence of impaired gp96 chaperone function. Our data indicate that Semapimod desensitizes TLR signaling via its effect on the TLR chaperone gp96. Fast inhibition by Semapimod is consistent with gp96 participating in high-affinity sensing of TLR ligands in addition to its role as a TLR chaperone.
Indexed as
Identifiers
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.