{
  "abstract": "Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) regulates necroptotic cell death and sterile inflammation, representing an established therapeutic target for degenerative and inflammatory disorders. Here, three putative hydantoin-based analogues bearing distinctive N-substitutions—an ethylcyclobutyl derivative (Compound 1), an ethoxyphenylethyl analogue (Compound 2), and a 5-chloroindole (3-fluoro-4-methylbenzyl) derivative (Compound 3)—were investigated against the prototypical inhibitor Necrostatin-1 using virtual screening, induced-fit docking, 500 ns molecular dynamics simulations and pharmacokinetic profiling. Induced Fit Docking within the RIPK1 kinase domain indicated that Compound 3 (−9.1 kcal/mol) and Compound 1 (−7.9 kcal/mol) achieved favorable predicted binding scores surpassing Necrostatin-1 (−7.3 kcal/mol), whereas Compound 2 displayed a considerably weaker binding score (−4.1 kcal/mol). All-atom molecular dynamics simulations revealed that Compound 1 maintained high dynamic stability with ligand RMSD constrained to 1.2–2.0 Å and sustained hydrogen bonding with Leu157. Conversely, Compound 2 dissociated from the primary binding pocket, while Compound 3 deviated from its initial docking pose (RMSD 7.0–9.2 Å) to engage a secondary interaction network with Asn170, Glu171 and Lys45. In silico ADME profiling predicted that all three candidates comply with Lipinski and Veber drug-likeness criteria with high predicted intestinal absorption. These computational findings provide putative structural insights into kinase-ligand interactions, prioritizing candidate molecules for chemical synthesis and in vitro biological evaluation.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Errikos Petsas",
      "orcid": "0009-0001-3805-6558"
    },
    {
      "affs": [
        0
      ],
      "name": "Christos T. Chasapis",
      "orcid": "0000-0002-8728-6245"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0c8e64r2ms82t.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219616",
  "fulltext_url": null,
  "id": "0c8e64r2ms82t",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9616",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1703|Computational Drug Discovery Methods"
    ]
  ],
  "openalex": "W7223907454",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-27",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/0c8e64r2ms82t.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27219616",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9616"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "Computational Evaluation of Necrostatin-1 Analogues as Potential RIPK1 Inhibitors",
  "title_text": "Computational Evaluation of Necrostatin-1 Analogues as Potential RIPK1 Inhibitors",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:57Z",
  "url": "https://research.draconitic.com/paper/0c8e64r2ms82t",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}