ArticleClinical and translational science2023
First-in-human phase 1 trial evaluating safety, pharmacokinetics, and pharmacodynamics of NLRP3 inflammasome inhibitor, GDC-2394, in healthy volunteers.
Article in Clinical and translational science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Advances in NLRP3 inflammasome research in viral infections: evolution, trends, and future directions.Frontiers in cellular and infection microbiology · 2026Pooled it
- First-in-human safety, tolerability, and pharmacokinetic results of DFV890, an oral low-molecular-weight NLRP3 inhibitor.Clinical and translational science · 2024Trial
- Mechanisms and therapeutic strategies of pyroptosis in sepsis‑induced acute lung injury (Review).International journal of molecular medicine · 2026Review
- Targeting NLRP3 with GDC-2394 ameliorates airway inflammation and smooth muscle hyperplasia in experimental asthma by suppressing the IL-6/JAK2/STAT3 axis.Scientific reports · 2026Article
- Deconstructing the Master Switch: Advances in Direct NLRP3 Inhibition.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Kinetic control of macrophage death by PTM-turnover crosstalk in infection and inflammation.Cell chemical biology · 2026Review
- Cofilin-1 is a redox-sensitive guard of the NLRP3 inflammasome.Nature immunology · 2026Article
- From mechanism to implementable benefit: decision-grade inflammasome modulation for Salmonella control.Molecular biology reports · 2026Article
- Caspase-1 in cancer and inflammatory diseases: a potential therapeutic target.Apoptosis : an international journal on programmed cell death · 2026Review
- The NLRP3 Inflammasome: Mechanisms of Activation, Regulation, and Therapeutic Opportunities.MedComm · 2026Review
- Advances in the mechanisms of the NLRP3 inflammasome in sepsis‑induced cardiomyopathy and targeted therapeutic studies (Review).Molecular medicine reports · 2026Review
- Progress in the Treatment of Ulcerative Colitis by Targeting NLRP3 Inflammasome.Drug design, development and therapy · 2026Review
- Targeting macrophages in liver fibrosis.Frontiers in immunology · 2026Review
- Profile of NT-0527, a brain penetrant NLRP3 Inflammasome inhibitor suitable as anRSC medicinal chemistry · 2025Article
- Genetic removal of Nlrp3 protects against age-related and R345W Efemp1-induced basal laminar deposit formation.Cell death & disease · 2025Article
- Inflammasome targeting for periodontitis prevention is sex dependent.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The neuroinflammatory triumvirate: NF-κB, NLRP3, and mTOR in spinal cord injury.Inflammopharmacology · 2025Review
- NLRP3 inflammasome: a key driver of neuroinflammation and a novel therapeutic target for neuropathic pain.Anesthesia and pain medicine · 2025Review
- Anti-Neuroinflammatory and Anti-Inflammatory Effects of the NLRP3 Inhibitor NT-0796 in Subjects with Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- MCC950 Alleviates Fat Embolism-Induced Acute Respiratory Distress Syndrome Through Dual Modulation of NLRP3 Inflammasome and ERK Pathways.International journal of molecular sciences · 2025Article
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inappropriate and chronic activation of the cytosolic NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome, a key component of innate immunity, likely underlies several inflammatory diseases, including coronary artery disease. This first-in-human phase I trial evaluated safety, pharmacokinetics (PKs), and pharmacodynamics (PDs) of oral, single (150-1800 mg) and multiple (300 or 900 mg twice daily for 7 days) ascending doses (SADs and MADs) of GDC-2394, a small-molecule inhibitor of NLRP3, versus placebo in healthy volunteers. The study also assessed the food effect on GDC-2394 and its CYP3A4 induction potential in food-effect (FE) and drug-drug interaction (DDI) stages, respectively. Although GDC-2394 was adequately tolerated in the SAD, MAD, and FE cohorts, two participants in the DDI stage experienced grade 4 drug-induced liver injury (DILI) deemed related to treatment, but unrelated to a PK drug interaction, leading to halting of the trial. Both participants experiencing severe DILI recovered within 3 months. Oral GDC-2394 was rapidly absorbed; exposure increased in an approximately dose-proportional manner with low-to-moderate intersubject variability. The mean terminal half-life ranged from 4.1 to 8.6 h. Minimal accumulation was observed with multiple dosing. A high-fat meal led to delays in time to maximum concentration and minor decreases in total exposure and maximum plasma concentration. GDC-2394 had minimal CYP3A4 induction potential with the sensitive CYP3A4 substrate, midazolam. Exploratory ex vivo whole-blood stimulation assays showed rapid, reversible, and near-complete inhibition of the selected PD biomarkers, IL-1β and IL-18, across all tested doses. Despite favorable PK and target engagement PD, the GDC-2394 safety profile precludes its further 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.