RARE DISEASE
Kawasaki disease
Kawasaki disease
Kawasaki disease
Synonyms: Mucocutaneous lymph node syndrome
Synonyms: Mucocutaneous lymph node syndrome
Synonyms: Mucocutaneous lymph node syndrome
Drug discovery
5
drugs
With orphan designations
Overview
Kawasaki disease (KD) is an acute, self-limiting vasculitis predominantly affecting children under 5 years, with potential coronary artery aneurysms (CAAs) in 25% of untreated cases [1][13]. Diagnosis requires ≥5 days of fever plus ≥4 of: bilateral conjunctivitis, oral mucosal changes, rash, extremity edema/erythema, and cervical lymphadenopathy [1][17]. Early treatment with intravenous immunoglobulin (IVIG) and aspirin reduces CAA risk to ~4% [5][13]. Refractory cases may require corticosteroids, TNF-α inhibitors, or other immunomodulators [1][5]. Long-term cardiovascular monitoring is critical for patients with CAAs [1][17].
Therapies
▪ First-line: IVIG (2 g/kg) + high-dose aspirin (80–100 mg/kg/day until afebrile) [1][11].
▪ Adjunctive therapies: Corticosteroids (for high-risk/refractory disease), TNF-α inhibitors (e.g., infliximab), or plasma exchange [5][15].
▪ Long-term: Low-dose aspirin (antiplatelet) ± anticoagulants for persistent aneurysms [3][13].
Categories: rare circulatory system diseases, rare systemic and rheumatological diseases, rare systemic or rheumatologic diseases of childhood
Research Papers
1,900 drug discovery papers related to Kawasaki disease, with 4 first-in-class and 1 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
1,900 drug discovery papers related to Kawasaki disease, with 4 first-in-class and 1 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-11 | FOS regulation of T-cell activation and the mechanism of inflammatory injury of coronary endothelium in Kawasaki disease.
Kawasaki disease (KD) is a pediatric systemic vasculitis often causing coronary lesions driven by aberrant T-cell activation. While FOS modulates T cells, its specific function in KD remains undefined. This study aims to investigate the role of FOS in T-cell activation and coronary endothelial inflammation in KD. The study integrated transcriptomic profiling of T cells from patients with KD and a murine model of Candida albicans water-soluble fraction (CAWS)-induced vasculitis to characterize FOS expression and vasculitis. Mechanistically, we employed lentiviral modulation of FOS in activated JURKAT cells co-cultured with human coronary artery endothelial cells (HCAECs) to delineate the impact of FOS on T-cell activation and endothelial inflammation. Compared to controls, FOS expression was significantly upregulated in peripheral blood T cells of acute KD patients (P<0.001). FOS levels were also elevated in peripheral blood T cells and cardiac inflammatory regions of the KD model mice, and inhibition of FOS expression attenuated vasculitis. CD3/28 magnetic bead stimulation increased FOS expression in JURKAT cells, along with elevated levels of inflammatory cytokines interleukin-6 and tumor necrosis factor. Co-culture of activated JURKAT cells with HCAECs resulted in marked endothelial inflammation. Conversely, knocking down FOS in JURKAT cells prior to activation and co-culture mitigated endothelial inflammation. FOS contributes to the development and progression of coronary endothelial inflammation in KD by modulating T-cell activation. Targeting FOS may represent a potential therapeutic strategy for mitigating KD-associated coronary artery injury.
2026-07-11 | Salidroside alleviates TNF-α-induced endothelial inflammatory injury by modulating NF-κB/NLRP3 inflammasome-related signaling: an integrated network pharmacology and experimental study.
Kawasaki disease (KD) is an acute febrile vasculitis in children, and vascular endothelial injury is a central event in the development of coronary artery lesions. Salidroside (SAL), a natural active compound extracted from Rhodiola rosea, has anti-inflammatory, anti-apoptotic, and immunomodulatory properties. However, its mechanism in KD-related vascular inflammatory injury remains unclear. This study aimed to investigate the protective effects and potential mechanisms of SAL in endothelial injury relevant to KD. Potential targets of SAL were predicted using reverse virtual screening and SwissTargetPrediction. KD-related targets were collected from the GeneCards and DisGeNET databases. Overlapping targets were subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction analyses. Key targets were further evaluated by molecular docking. Human coronary artery endothelial cells (HCAECs) were stimulated with tumor necrosis factor-α (TNF-α) to establish an endothelial inflammatory injury model. RNA-sequencing (RNA-seq) was performed to identify differentially expressed genes after SAL treatment. The protective effects of SAL were then assessed by Cell Counting Kit-8 assay, wound-healing assay, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) flow cytometry, reverse transcription quantitative polymerase chain reaction, and western blotting. Network pharmacology identified 226 potential SAL targets and 2,686 KD-related targets, with 56 overlapping targets. KEGG enrichment and RNA-seq indicated that SAL may regulate a broader inflammatory network, particularly interleukin (IL)-17 and TNF signaling pathways. Molecular docking showed stable binding of SAL to matrix metalloproteinase-9 (MMP-9). In TNF-α-stimulated HCAECs, SAL significantly improved cell viability, inhibited excessive migration, and reduced inflammatory cell death. SAL also decreased the messenger RNA (mRNA) expression of IL-1β, IL-6, MMP-9, interleukin-17 receptor A (IL-17RA), intercellular adhesion molecule-1 (ICAM-1), and NOD-like receptor family pyrin domain containing 3 (NLRP3), and reduced the protein levels of IL-6, phosphorylated nuclear factor kappa B (NF-κB) p65, NLRP3, gasdermin D (GSDMD), and Caspase-1 (P<0.05). SAL alleviates TNF-α-induced endothelial inflammatory injury in HCAECs. Its protective effects are associated with suppression of inflammatory signaling, inhibition of abnormal migration and cell death, and attenuation of NF-κB/NLRP3 inflammasome-related molecules. These findings provide preliminary experimental evidence for further investigation of SAL in KD-related vascular inflammation.
2026-07-09 | Immune regulatory mechanisms and potential microbiota-associated targets in Kawasaki disease: an integrative multi-omics and network pharmacology study.
Kawasaki disease (KD) is a systemic vasculitis in children primarily affecting the coronary arteries, and studies suggest that the gut microbiota may be involved in KD pathogenesis, inflammatory responses, and immune regulation. This study employed an integrative multi-omics strategy to systematically investigate gut microbiota-metabolite interactions in KD. Key molecular targets were identified using network-based analyses and machine learning models, with Mendelian randomization providing causal validation. Single-cell transcriptomics and molecular docking further elucidated immune cell interactions and metabolite-protein binding, highlighting critical regulatory pathways. We identified SELP as a core molecular target in KD, predominantly expressed in platelets and involved in immune and inflammatory responses. Gut microbiota-derived metabolites, including palmitoylethanolamide, pantothenic acid, and 1-O-caffeoylglycerol, may regulate immune cell interactions via the RESISTIN signalling pathway. Altered abundances of microbial taxa such as Bacteroides, Parabacteroides, and Bifidobacterium suggest their potential role in inflammation modulation. Activation of IL-17, TNF, MAPK, and PI3K-Akt pathways further contributes to disease progression, highlighting the microbiota-metabolite-SELP axis as a potential therapeutic target in KD. These findings lay the groundwork for subsequent in vitro and in vivo studies, advancing the development of microbiome-based intervention strategies.
2026-07-11 | FOS regulation of T-cell activation and the mechanism of inflammatory injury of coronary endothelium in Kawasaki disease.
Kawasaki disease (KD) is a pediatric systemic vasculitis often causing coronary lesions driven by aberrant T-cell activation. While FOS modulates T cells, its specific function in KD remains undefined. This study aims to investigate the role of FOS in T-cell activation and coronary endothelial inflammation in KD. The study integrated transcriptomic profiling of T cells from patients with KD and a murine model of Candida albicans water-soluble fraction (CAWS)-induced vasculitis to characterize FOS expression and vasculitis. Mechanistically, we employed lentiviral modulation of FOS in activated JURKAT cells co-cultured with human coronary artery endothelial cells (HCAECs) to delineate the impact of FOS on T-cell activation and endothelial inflammation. Compared to controls, FOS expression was significantly upregulated in peripheral blood T cells of acute KD patients (P<0.001). FOS levels were also elevated in peripheral blood T cells and cardiac inflammatory regions of the KD model mice, and inhibition of FOS expression attenuated vasculitis. CD3/28 magnetic bead stimulation increased FOS expression in JURKAT cells, along with elevated levels of inflammatory cytokines interleukin-6 and tumor necrosis factor. Co-culture of activated JURKAT cells with HCAECs resulted in marked endothelial inflammation. Conversely, knocking down FOS in JURKAT cells prior to activation and co-culture mitigated endothelial inflammation. FOS contributes to the development and progression of coronary endothelial inflammation in KD by modulating T-cell activation. Targeting FOS may represent a potential therapeutic strategy for mitigating KD-associated coronary artery injury.
2026-07-11 | Salidroside alleviates TNF-α-induced endothelial inflammatory injury by modulating NF-κB/NLRP3 inflammasome-related signaling: an integrated network pharmacology and experimental study.
Kawasaki disease (KD) is an acute febrile vasculitis in children, and vascular endothelial injury is a central event in the development of coronary artery lesions. Salidroside (SAL), a natural active compound extracted from Rhodiola rosea, has anti-inflammatory, anti-apoptotic, and immunomodulatory properties. However, its mechanism in KD-related vascular inflammatory injury remains unclear. This study aimed to investigate the protective effects and potential mechanisms of SAL in endothelial injury relevant to KD. Potential targets of SAL were predicted using reverse virtual screening and SwissTargetPrediction. KD-related targets were collected from the GeneCards and DisGeNET databases. Overlapping targets were subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction analyses. Key targets were further evaluated by molecular docking. Human coronary artery endothelial cells (HCAECs) were stimulated with tumor necrosis factor-α (TNF-α) to establish an endothelial inflammatory injury model. RNA-sequencing (RNA-seq) was performed to identify differentially expressed genes after SAL treatment. The protective effects of SAL were then assessed by Cell Counting Kit-8 assay, wound-healing assay, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) flow cytometry, reverse transcription quantitative polymerase chain reaction, and western blotting. Network pharmacology identified 226 potential SAL targets and 2,686 KD-related targets, with 56 overlapping targets. KEGG enrichment and RNA-seq indicated that SAL may regulate a broader inflammatory network, particularly interleukin (IL)-17 and TNF signaling pathways. Molecular docking showed stable binding of SAL to matrix metalloproteinase-9 (MMP-9). In TNF-α-stimulated HCAECs, SAL significantly improved cell viability, inhibited excessive migration, and reduced inflammatory cell death. SAL also decreased the messenger RNA (mRNA) expression of IL-1β, IL-6, MMP-9, interleukin-17 receptor A (IL-17RA), intercellular adhesion molecule-1 (ICAM-1), and NOD-like receptor family pyrin domain containing 3 (NLRP3), and reduced the protein levels of IL-6, phosphorylated nuclear factor kappa B (NF-κB) p65, NLRP3, gasdermin D (GSDMD), and Caspase-1 (P<0.05). SAL alleviates TNF-α-induced endothelial inflammatory injury in HCAECs. Its protective effects are associated with suppression of inflammatory signaling, inhibition of abnormal migration and cell death, and attenuation of NF-κB/NLRP3 inflammasome-related molecules. These findings provide preliminary experimental evidence for further investigation of SAL in KD-related vascular inflammation.
2026-07-09 | Immune regulatory mechanisms and potential microbiota-associated targets in Kawasaki disease: an integrative multi-omics and network pharmacology study.
Kawasaki disease (KD) is a systemic vasculitis in children primarily affecting the coronary arteries, and studies suggest that the gut microbiota may be involved in KD pathogenesis, inflammatory responses, and immune regulation. This study employed an integrative multi-omics strategy to systematically investigate gut microbiota-metabolite interactions in KD. Key molecular targets were identified using network-based analyses and machine learning models, with Mendelian randomization providing causal validation. Single-cell transcriptomics and molecular docking further elucidated immune cell interactions and metabolite-protein binding, highlighting critical regulatory pathways. We identified SELP as a core molecular target in KD, predominantly expressed in platelets and involved in immune and inflammatory responses. Gut microbiota-derived metabolites, including palmitoylethanolamide, pantothenic acid, and 1-O-caffeoylglycerol, may regulate immune cell interactions via the RESISTIN signalling pathway. Altered abundances of microbial taxa such as Bacteroides, Parabacteroides, and Bifidobacterium suggest their potential role in inflammation modulation. Activation of IL-17, TNF, MAPK, and PI3K-Akt pathways further contributes to disease progression, highlighting the microbiota-metabolite-SELP axis as a potential therapeutic target in KD. These findings lay the groundwork for subsequent in vitro and in vivo studies, advancing the development of microbiome-based intervention strategies.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
5 orphan drug designations for Kawasaki disease.
5 orphan drug designations for Kawasaki disease.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Infliximab | antibodies | EMA | 2026-05-20 | — | Oddifact |
acetylsalicylic acid | small molecules | FDA | 2025-12-19 | — | Academic Pharmaceuticals Inc. |
infliximab | antibodies | FDA | 2024-07-26 | — | ODDIFACT SAS |
aspirin for injection (acetylsalicylic acid) | small molecules | FDA | 2020-09-18 | — | Rhoshan Pharmaceuticals Inc. |
Ulinastatin | small molecules | FDA | 2020-06-12 | — | RNR BioMedical Inc. |
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