ArticleScientific reports2019
Small Molecule IL-36γ Antagonist as a Novel Therapeutic Approach for Plaque Psoriasis.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 67 citations in OpenAlex.
- Advances in targeting IL-1 family cytokines for the treatment of inflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Advances in Bioprinting to Model Immune-Mediated Skin Diseases.Advanced healthcare materials · 2026Review
- IL-36 participated in airway remodeling in chronic asthma model by inducing epithelial-mesenchymal transition process.European journal of medical research · 2026Article
- Balancing efficacy and hepatotoxicity: a comprehensive review of oral medications in psoriasis management.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Systemic Psoriasis: From Molecular Mechanisms to Global Management Strategies.Clinical reviews in allergy & immunology · 2025Review
- Considerations for defining and diagnosing generalized pustular psoriasis.Journal of the European Academy of Dermatology and Venereology : JEADV · 2025Review
- Skin-Protective Performance of Alternative Stratum Corneum Formed by a Pseudo-Ceramide-Containing Steroid Lamellar Cream.Experimental dermatology · 2025Article
- Updated genetic background of generalized pustular psoriasis as an autoinflammatory keratinization disease.The Journal of dermatology · 2025Review
- Discovery of selective low molecular weight interleukin-36 receptor antagonists by encoded library technologies.Nature communications · 2025Article
- Pharmacological Management of Psoriasis: Current Landscape and Future Perspectives.Recent advances in inflammation & allergy drug discovery · 2025Review
- Biologics and small molecules for psoriasis: current and future progress.Drugs in context · 2025Review
- Mossy Fiber Sprouting in Temporal Lobe Epilepsy: The Impact of Netrin-1, DCC, and Gene Expression Changes.Biomedicines · 2024Article
- In Silico and In Vitro Analysis of IL36RN Alterations Reveals Critical Residues for the Function of the Interleukin-36 Receptor Complex.The Journal of investigative dermatology · 2023Article
- Discovery of a selective and biologically active low-molecular weight antagonist of human interleukin-1β.Nature communications · 2023Article
- Challenges and Future Trends in the Treatment of Psoriasis.International journal of molecular sciences · 2023Review
- Genetics of Generalized Pustular Psoriasis: Current Understanding and Implications for Future Therapeutics.Genes · 2023Review
- Serum Interleukin-36 α as a Candidate Biomarker to Distinguish Behçet's Syndrome and Psoriatic Arthritis.International journal of molecular sciences · 2023Article
- Targeting IL-36 in Inflammatory Skin Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Article
- The role of the interleukin-36 axis in generalized pustular psoriasis: a review of the mechanism of action of spesolimab.Frontiers in immunology · 2023Review
- IL-17A-driven psoriasis is critically dependent on IL-36 signaling.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
25 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IL-36 cytokines are pro-inflammatory members of the IL-1 family that are upregulated in inflammatory disorders. Specifically, IL-36γ is highly expressed in active psoriatic lesions and can drive pro-inflammatory processes in 3D human skin equivalents supporting a role for this target in skin inflammation. Small molecule antagonists of interleukins have been historically challenging to generate. Nevertheless, we performed a small molecule high-throughput screen to identify IL-36 antagonists using a novel TR-FRET binding assay. Several compounds, including 2-oxypyrimidine containing structural analogs of the marketed endothelin receptor A antagonist Ambrisentan, were identified as hits from the screen. A-552 was identified as a the most potent antagonist of human IL-36γ, but not the closely related family member IL-36α, was capable of attenuating IL-36γ induced responses in mouse and human disease models. Additionally, x-ray crystallography studies identified key amino acid residues in the binding pocket present in human IL-36γ that are absent in human IL-36α. A-552 represents a first-in-class small molecule antagonist of IL-36 signaling that could be used as a chemical tool to further investigate the role of this pathway in inflammatory skin diseases such as psoriasis.
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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.