ArticleThe Journal of experimental medicine2018
Selective inhibition of the p38α MAPK-MK2 axis inhibits inflammatory cues including inflammasome priming signals.
Article in The Journal of experimental medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Pooled it
- CC-99677, a novel, oral, selective covalent MK2 inhibitor, sustainably reduces pro-inflammatory cytokine production.Arthritis research & therapy · 2022Trial
- Post-translational modifications in Neuroimmune cells during neuroinflammation: integrated regulatory networks and therapeutic opportunities.Biology direct · 2026Review
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- Article
- The Antipsychotic Aripiprazole Induces Cytotoxicity in Bladder Cancer Cells While Preserving Urothelial and Bladder Function.Pharmacology research & perspectives · 2026Article
- Indirect inhibition of the NLRP3-interleukin-1β axis contributes to the efficacy of JAK1 inhibitors in experimental colitis and human ulcerative colitis.Nature communications · 2026Article
- MK2/p38/p53 Suppress Basal IL-1β and Non-Canonical NF-κB Signaling in Macrophages.International journal of molecular sciences · 2026Article
- Preclinical Pharmacokinetics, ADME, and Drug-Drug Interaction Evaluation of S024, a Novel p38/MK2 Inhibitor for Rheumatoid Arthritis.Drug design, development and therapy · 2026Article
- Non-Catalytic Inhibitors of the p38/MK2 Interface: Repurposing Approved Drugs to Target Neuroinflammation in Alzheimer's Disease.Journal of medicinal chemistry · 2025Article
- Article
- Article
- MK2 Inhibition in CD4+ T Cells Protects Against IFNγ and IL-17A, Chronic Inflammation, and Fibrosis in Inflammatory Bowel Disease Models.Inflammatory bowel diseases · 2025Article
- COPS5 Triggers Ferroptosis Defense by Stabilizing MK2 in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Proanthocyanidin capsules remodel the ROS microenvironment via regulating MAPK signaling for accelerating diabetic wound healing.Materials today. Bio · 2025Article
- Article
- Targeted degradation of MK2 is insufficient to block inflammatory cytokine production in human cells due to cooperativity with MK3 and MK5.Frontiers in immunology · 2025Article
- Article
- Interrogating endothelial barrier regulation by temporally resolved kinase network generation.Life science alliance · 2024Article
- Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
p38α activation of multiple effectors may underlie the failure of global p38α inhibitors in clinical trials. A unique inhibitor (CDD-450) was developed that selectively blocked p38α activation of the proinflammatory kinase MK2 while sparing p38α activation of PRAK and ATF2. Next, the hypothesis that the p38α-MK2 complex mediates inflammasome priming cues was tested. CDD-450 had no effect on NLRP3 expression, but it decreased IL-1β expression by promoting IL-1β mRNA degradation. Thus, IL-1β is regulated not only transcriptionally by NF-κB and posttranslationally by the inflammasomes but also posttranscriptionally by p38α-MK2. CDD-450 also accelerated TNF-α and IL-6 mRNA decay, inhibited inflammation in mice with cryopyrinopathy, and was as efficacious as global p38α inhibitors in attenuating arthritis in rats and cytokine expression by cells from patients with cryopyrinopathy and rheumatoid arthritis. These findings have clinical translation implications as CDD-450 offers the potential to avoid tachyphylaxis associated with global p38α inhibitors that may result from their inhibition of non-MK2 substrates involved in antiinflammatory and housekeeping responses.
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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.