{
  "abstract": "An integrated computational workflow was developed to prioritize piperazinylanthranilamide factor Xa (FXa) inhibitor candidates. Twenty literature compounds were geometry-optimized and described using alvaDesc to construct a constrained additive multivariate adaptive regression splines model. Internal validation and an assessment of the applicability domain guided the evaluation of 20 prospective analogs. Ten selected analogs and two same-series references were docked to FXa, with apixaban as the crystallographic comparator. Thirteen initial 100 ns molecular dynamics simulations were supplemented by two independent runs for each of PAX-M09, PAX-M15, and PAX-M18. Binding energetics were assessed using molecular mechanics/generalized Born surface area (MM/GBSA), alongside in silico developability profiling. The model achieved R2 = 0.904 and an internal leave-one-out Q2 of 0.846. PAX-M09 was the strongest strict in-domain prediction, whereas PAX-M15 was borderline. Apixaban redocking yielded a root-mean-square deviation (RMSD) of 0.953 Å. Although PAX-M17 and PAX-M19 ranked highest in docking, subsequent analyses prioritized PAX-M15, PAX-M09, and PAX-M18. PAX-M15 showed the most consistent positional behavior across replicates and consistently favorable run-specific MM/GBSA estimates (−68.76, −70.11, and −69.42 kcal/mol). PAX-M09 and PAX-M18 showed greater between-run heterogeneity. Solubility, metabolic, and toxicity liabilities remained important. The results support experimental investigation of the three candidates without changing their applicability-domain classifications or establishing superior experimental potency.",
  "abstract_shown": true,
  "affiliations": [
    "University of Health Sciences in Bydgoszcz, Jagiellońska 4 Str., 85-067 Bydgoszcz, Poland",
    "Department of Toxicology and Bromatology, Faculty of Pharmacy, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, A. Jurasza 2 Street, 85-089 Bydgoszcz, Poland",
    "Doctoral School of Medical and Health Sciences, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University in Toruń, Jagiellońska 13-15 Str., 85-067 Bydgoszcz, Poland",
    "Department of Pharmaceutical Chemistry and Biomaterials, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Str., 02-093 Warsaw, Poland",
    "Department of Organic and Physical Chemistry, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Paweł Gordon",
      "orcid": "0009-0007-7926-8753"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Michał Janiak"
    },
    {
      "affs": [
        1
      ],
      "name": "Marcin Gackowski",
      "orcid": "0000-0001-9176-7108"
    },
    {
      "affs": [
        3
      ],
      "name": "Monika Zielińska-Pisklak",
      "orcid": "0000-0002-4457-6381"
    },
    {
      "affs": [
        4
      ],
      "name": "Łukasz Szeleszczuk",
      "orcid": "0000-0002-5302-3797"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8q4bj5srjwn80.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27209204",
  "fulltext_url": "https://europepmc.org/articles/PMC13705391",
  "id": "8q4bj5srjwn80",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/20/9204",
  "language": "eng",
  "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": "W7222536183",
  "pdf_url": "https://europepmc.org/articles/PMC13705391?pdf=render",
  "pmcid": "PMC13705391",
  "pmid": "42941974",
  "published": "2026-10-16",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/8q4bj5srjwn80.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27209204",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/20/9204"
    },
    {
      "first_seen": "2026-10-30T12:22:12Z",
      "native_id": "MED:42941974",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42941974"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "QSAR-Guided In Silico Design of Piperazinylanthranilamide Factor Xa Inhibitors: Applicability-Domain Assessment, ADMET Profiling, Molecular Docking, Molecular Dynamics, and MM/GBSA",
  "title_text": "QSAR-Guided In Silico Design of Piperazinylanthranilamide Factor Xa Inhibitors: Applicability-Domain Assessment, ADMET Profiling, Molecular Docking, Molecular Dynamics, and MM/GBSA",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:12Z",
  "url": "https://research.draconitic.com/paper/8q4bj5srjwn80",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}