{
  "abstract": "Nicotinonitriles (3-cyanopyridine-based compounds) are emerging as privileged frameworks in rational anticancer drug discovery due to their distinctive electronic properties, metabolic stability, and diverse pharmacological profiles. This review discusses recent developments in nicotinonitrile-derived agents as effective kinase inhibitors of EGFR, VEGFR-2, HER2, CDKs, c-Met, BRAF, and PIM kinases, among others. By discussing mono-, bi-, and multi-target inhibitors, the mechanisms of action are reviewed, with adaptations to induce apoptosis, arrest the cell cycle, and reverse drug resistance. Many clinical and preclinical candidates are nanomolar to sub-micromolar in equipotency across multiple cancer models. The substitution at the core of nicotinonitrile improves targeted selectivity, drug-like properties, and the safety profile, and is a key toward next-generation anticancer agents. Moreover, the review presents information on enzyme-mediated inhibition, hybrid construction, and molecular docking that strengthen the scaffold's potential for ecotoxicological pipelines. Overall, nicotinonitrile-based derivatives seem to be an attractive nucleus for multi-target drug discovery, with a broad therapeutic spectrum in cancer management.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, College of Sciences, University of Sharjah Sharjah 27272 United Arab Emirates mohamed.elsayed@sharjah.ac.ae.",
    "Bioinformatics and Functional Genomics Research Group, Research Institute of Sciences and Engineering (RISE), University of Sharjah Sharjah 27272 United Arab Emirates.",
    "Chemistry Department, Faculty of Science, Suez Canal University Ismailia 41522 Egypt.",
    "Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University-Egypt New Damietta 34518 Egypt.",
    "Department of Pharmacy, Institute of Pharmaceutics and Biopharmaceutics, Marburg University Robert-Koch-Str. 4 35037 Marburg Germany sherif.fahmy@pharmazie.uni-marburg.de.",
    "Pest Physiology Department, Plant Protection Research Institute, Agricultural Research Center Giza 12311 Egypt.",
    "Department of Medicinal Chemistry, Faculty of Pharmacy, Galala University New Galala 43713 Egypt asmaa.yassen@gu.edu.eg.",
    "Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University Ismailia 41522 Egypt.",
    "Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University Ismailia 41522 Egypt."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Mohamed S Nafie",
      "orcid": "0000-0003-4454-6390"
    },
    {
      "affs": [
        3
      ],
      "name": "Mohamed A Zeidan",
      "orcid": "0009-0001-4191-4146"
    },
    {
      "affs": [
        4
      ],
      "name": "Sherif Ashraf Fahmy",
      "orcid": "0000-0003-3056-8281"
    },
    {
      "affs": [
        5
      ],
      "name": "Mohamed K Diab",
      "orcid": "0000-0001-7879-1357"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Khaled M Darwish",
      "orcid": "0000-0002-0597-482X"
    },
    {
      "affs": [
        6,
        8
      ],
      "name": "Asmaa S A Yassen",
      "orcid": "0000-0002-7956-9739"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0mcm15hx0w7kd.bib",
  "cited_by": 0,
  "doi": "10.1039/d6ra05778k",
  "fulltext_url": "https://europepmc.org/articles/PMC13684883",
  "id": "0mcm15hx0w7kd",
  "issns": [
    "2046-2069"
  ],
  "landing_url": "https://europepmc.org/article/MED/42910047",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Chemistry"
    ],
    [
      "openalex",
      "1605|Synthesis and biological activity"
    ]
  ],
  "openalex": "W7223138864",
  "pdf_url": "https://europepmc.org/articles/PMC13684883?pdf=render",
  "pmcid": "PMC13684883",
  "pmid": "42910047",
  "published": "2026-10-21",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/0mcm15hx0w7kd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "MED:42910047",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42910047"
    },
    {
      "first_seen": "2026-11-07T12:23:37Z",
      "native_id": "PMC13684883",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6ra05778k"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Synthesis and biological activity",
      "subfield": "organic"
    }
  ],
  "title": "Nicotinonitriles-based therapeutics as versatile pharmacophores in rational anticancer drug design.",
  "title_text": "Nicotinonitriles-based therapeutics as versatile pharmacophores in rational anticancer drug design.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:05Z",
  "url": "https://research.draconitic.com/paper/0mcm15hx0w7kd",
  "venue": "RSC advances",
  "versions": []
}