{
  "abstract": "Colorectal cancer (CRC) remains one of the most prevalent malignancies globally. Despite significant advancements in targeted therapies, drug resistance and therapeutic target mutations continue to pose challenges. Consequently, identifying novel therapeutic targets and developing related compounds are essential for discovering new CRC treatment strategies. The RIO Kinase 1 (RIOK1) protein has emerged as a potential anti-tumor target, playing a critical role in eukaryotic ribosomal biosynthesis and modulating cellular proliferation. However, few compounds have been designed to target RIOK1, and the antitumor activity of RIOK1 inhibitors has yet to be thoroughly investigated. In this study, we report the optimization of pyridine caffeic acid benzyl amide derivatives as RIOK1 inhibitors and identified CINS-1 as a potent compound with markedly enhanced binding affinity for AfRIOK1 and RIOK1. Notably, we elucidated the crystal structure of AfRIOK1 in complex with CINS-1. Our findings further confirm the inhibitory effects of CINS-1 on CRC cell proliferation both in vitro and in vivo. Additionally, CINS-1 was shown to disrupt ribosomal biosynthesis by hindering 18S maturation and triggering a P53-mediated nucleolar stress response. Overall, these results provide a theoretical and empirical basis for considering the RIOK1 inhibitor CINS-1 as a promising candidate for anti-CRC therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.",
    "NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Department of Pharmacy, Pingshan Hospital, Southern Medical University, Shenzhen 518100, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ying Jiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Chuan Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Fang Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Guolong Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Shanhe Wan"
    },
    {
      "affs": [
        0
      ],
      "name": "Yongxin Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Ruohong Yan"
    },
    {
      "affs": [
        0
      ],
      "name": "Zichao Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuanxin Tian"
    },
    {
      "affs": [
        0
      ],
      "name": "Tingting Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoyun Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Le Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Shaoyu Wu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shuwen Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianjun Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiajie Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4kg1ab21pk3jt.bib",
  "cited_by": 0,
  "doi": "10.1016/j.apsb.2026.07.004",
  "fulltext_url": "https://europepmc.org/articles/PMC13712371",
  "id": "4kg1ab21pk3jt",
  "issns": [
    "2211-3835",
    "2211-3843"
  ],
  "landing_url": "https://europepmc.org/article/MED/42948403",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "1605|Synthesis and biological activity"
    ]
  ],
  "openalex": "W7167669458",
  "pdf_url": "https://europepmc.org/articles/PMC13712371?pdf=render",
  "pmcid": "PMC13712371",
  "pmid": "42948403",
  "published": "2026-07-08",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/4kg1ab21pk3jt.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:36Z",
      "native_id": "MED:42948403",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42948403"
    },
    {
      "first_seen": "2026-10-31T12:22:58Z",
      "native_id": "PMC13712371",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.apsb.2026.07.004"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Synthesis and biological activity",
      "subfield": "organic"
    }
  ],
  "title": "Discovery of a small molecule RIOK1 inhibitor CINS-1 against colorectal cancer via disrupting ribosomal biosynthesis.",
  "title_text": "Discovery of a small molecule RIOK1 inhibitor CINS-1 against colorectal cancer via disrupting ribosomal biosynthesis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:58Z",
  "url": "https://research.draconitic.com/paper/4kg1ab21pk3jt",
  "venue": "Acta pharmaceutica Sinica. B",
  "versions": []
}