Trial reportArthritis research & therapy2022
CC-99677, a novel, oral, selective covalent MK2 inhibitor, sustainably reduces pro-inflammatory cytokine production.
Trial report in Arthritis research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03554993 (A Phase I, Randomized, Single-center, 3-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of CC 99677 in Healthy Adult Subjects), which is not on this map. Cited by 16 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.
A Phase I, Randomized, Single-center, 3-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of CC 99677 in Healthy Adult Subjects
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Pooled it
- Phase II randomised, placebo-controlled study to evaluate the efficacy and safety of an MK2 inhibitor in ankylosing spondylitis.RMD open · 2026Trial
- Exploring the nexus between inflammation and mobility through the lens of healthy aging: current scenario and future perspectives.Aging clinical and experimental research · 2026Review
- Immunometabolic control of macrophage plasticity in wound healing: mechanistic insights and therapeutic opportunities.Frontiers in immunology · 2026Review
- Characterization of the Second-Generation Covalent Fragment Library (CovLib Gen2): Thiol Reactivity Profiling and p53-Y220C Rescue.Drug design, development and therapy · 2026Article
- Qing-Xin-Jie-Yu Granule attenuates myocardial infarction-induced inflammatory response by regulating the MK2/TTP pathway.Pharmaceutical biology · 2025Article
- Article
- Exploring the molecular mechanism of Epimedium for the treatment of ankylosing spondylitis based on network pharmacology, molecular docking, and molecular dynamics simulations.Molecular diversity · 2025Article
- 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
- Based on the Dual Pathway of Interaction-Mediated NF-κB in Cell Apoptosis and Immune Inflammation to Study the Effect of Danzhi Xiaoyao Powder on the Learning and Cognitive Ability of AD Model Rats.Degenerative neurological and neuromuscular disease · 2025Article
- Targeting radiotherapy-induced inflammation in cancer metastasis: insights into immune modulation, therapeutic opportunities and radiogenomics.Frontiers in oncology · 2025Review
- Pharmacological Management of Psoriasis: Current Landscape and Future Perspectives.Recent advances in inflammation & allergy drug discovery · 2025Review
- Exploring 2-Sulfonylpyrimidine Warheads as Acrylamide Surrogates for Targeted Covalent Inhibition: A BTK Story.Journal of medicinal chemistry · 2024Article
- Cellular Senescence and Inflammaging in the Bone: Pathways, Genetics, Anti-Aging Strategies and Interventions.International journal of molecular sciences · 2024Review
- Protein kinases: drug targets for immunological disorders.Nature reviews. Immunology · 2023Review
- Revisiting p38 Mitogen-Activated Protein Kinases (MAPK) in Inflammatory Arthritis: A Narrative of the Emergence of MAPK-Activated Protein Kinase Inhibitors (MK2i).Pharmaceuticals (Basel, Switzerland) · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMitogen-activated protein kinase (MAPK)-activated protein kinase-2 (MK2) is activated downstream of p38 MAPK and regulates stability of mRNAs encoding inflammatory cytokines. CC-99677 is a novel, irreversible, covalent MK2 inhibitor under development for the treatment of ankylosing spondylitis (AS) and other inflammatory diseases. As part of a phase I clinical trial to assess safety and tolerability, we evaluated target engagement, pharmacokinetics, and pharmacodynamics of CC-99677.
methodsThe MK2 inhibitor CC-99677 was evaluated for its effect on cytokine expression in vitro in peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with a definitive AS diagnosis. A novel in vitro model was developed to compare the potential for tachyphylaxis of CC-99677 and p38 inhibitors in THP-1 cells. The effect of CC-99677 on tristetraprolin (TTP) and cytokine mRNA was assessed in stimulated human monocyte-derived macrophages. In a first-in-human study, thirty-seven healthy volunteers were randomly assigned to daily oral doses of CC-99677 or placebo, and blood was collected at pre-specified time points before and after dosing. CC-99677 concentrations were assessed in the plasma, and CC-99677 binding to MK2 was evaluated in PBMCs. Ex vivo stimulation of the whole blood was conducted from participants in the first-in-human study to assess the pharmacodynamic effects.
resultsIn vitro, CC-99677 inhibited tumor necrosis factor (TNF), interleukin (IL)-6, and IL-17 protein production in samples of monocytes and macrophages from AS patients and healthy volunteers via an mRNA-destabilization mechanism. In the in vitro model of tachyphylaxis, CC-99677 showed a differentiated pattern of sustained TNF protein inhibition compared with p38 inhibitors. CC-99677 reduced TTP phosphorylation and accelerated the decay of inflammatory cytokine mRNA in lipopolysaccharide-stimulated macrophages. Administration of CC-99677 to healthy volunteers was safe and well-tolerated, with linear pharmacokinetics and sustained reduction of ex vivo whole blood TNF, IL-6, and chemokine synthesis.
conclusionsCC-99677 inhibition of MK2 is a promising approach for the treatment of inflammatory diseases and may overcome the limitations of p38 MAPK inhibition.
trial registrationClinicalTrials.gov NCT03554993 .
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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.