{
  "abstract": "BLU-451 is a potent and selective tyrosine kinase inhibitor designed to target uncommon epidermal growth factor receptor (EGFR) mutations, spare wild-type (WT) EGFR, and be active in the central nervous system (CNS). In vitro EGFR enzyme assays and engineered cell line models revealed selectivity and antiproliferative potency of BLU-451 against a wide range of EGFR mutations in non–small cell lung cancer, including common mutations, atypical mutations, and exon 20 insertions. Particularly, BLU-451 demonstrated robust antitumor activity in EGFR exon 20 insertion cell-derived and patient-derived xenograft models and was well tolerated in animal studies. Pharmacokinetic and pharmacodynamic analyses showed that BLU-451 suppressed exon 20 insertion phosphorylated EGFR expression levels within tumor tissues but not in skin and intestinal tissues, potentially indicative of lower toxicity associated with WT EGFR. In intracranial tumor models with imaging-based analyses, BLU-451 showed CNS antitumor efficacy. Early clinical data from patients enrolled in the phase I portion of the phase I/II CONCERTO trial (NCT05241873) demonstrated the overall clinical potential of BLU-451, including its CNS antitumor activity in patients with EGFR exon 20 insertions and atypical mutations. Initial data suggest that BLU-451 is an active molecule. Further evaluation of the safety profile and pharmacokinetic properties of BLU-451 is needed.",
  "abstract_shown": true,
  "affiliations": [
    "Blueprint Medicines Corporation, Cambridge, Massachusetts.",
    "Virginia Cancer Specialists Research Institute, Fairfax, Virginia.",
    "Division of Hematology and Oncology, University of Washington School of Medicine, Seattle, Washington.",
    "Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.",
    "NYU Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, New York.",
    "Tempus AI, Chicago, Illinois.",
    "Department of Medical Oncology and Therapeutics Research, City of Hope, Irvine, California.",
    "Dana-Farber Cancer Institute, Boston, Massachusetts.",
    "Massachusetts General Hospital Cancer Center, Boston, Massachusetts.",
    "Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.",
    "Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.",
    "Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.",
    "Department of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.",
    "Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.",
    "Department of Thoracic-Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yves A. Millet",
      "orcid": "0000-0002-7001-7030"
    },
    {
      "affs": [
        1
      ],
      "name": "Alexander I. Spira",
      "orcid": "0000-0003-1303-0447"
    },
    {
      "affs": [
        2
      ],
      "name": "Christina S. Baik",
      "orcid": "0009-0007-0822-9060"
    },
    {
      "affs": [
        3
      ],
      "name": "Min Hee Hong",
      "orcid": "0000-0003-3490-2195"
    },
    {
      "affs": [
        4
      ],
      "name": "Elaine Shum",
      "orcid": "0000-0002-0390-5716"
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    {
      "affs": [
        5
      ],
      "name": "Jyoti D. Patel",
      "orcid": "0000-0002-7550-2094"
    },
    {
      "affs": [
        6
      ],
      "name": "Danny Nguyen",
      "orcid": "0000-0002-2479-2271"
    },
    {
      "affs": [
        7
      ],
      "name": "Pasi A. Jänne",
      "orcid": "0000-0002-7821-4928"
    },
    {
      "affs": [
        8
      ],
      "name": "Zofia Piotrowska",
      "orcid": "0000-0002-9008-8573"
    },
    {
      "affs": [
        9
      ],
      "name": "Natasha B. Leighl",
      "orcid": "0000-0002-3249-4602"
    },
    {
      "affs": [
        10
      ],
      "name": "Shingo Matsumoto",
      "orcid": "0000-0001-9627-5401"
    },
    {
      "affs": [
        11
      ],
      "name": "Lova Sun",
      "orcid": "0000-0002-5015-2964"
    },
    {
      "affs": [
        12
      ],
      "name": "Tsung-Ying Yang",
      "orcid": "0000-0003-0198-1077"
    },
    {
      "affs": [
        13
      ],
      "name": "Tatsuya Yoshida",
      "orcid": "0000-0003-4896-5824"
    },
    {
      "affs": [
        14
      ],
      "name": "Monique B. Nilsson",
      "orcid": "0000-0002-0975-8833"
    },
    {
      "affs": [
        14
      ],
      "name": "John V. Heymach",
      "orcid": "0000-0001-9068-8942"
    },
    {
      "affs": [
        0
      ],
      "name": "Brion W. Murray",
      "orcid": "0000-0003-1591-2566"
    },
    {
      "affs": [
        0
      ],
      "name": "Jeffrey Keats",
      "orcid": "0009-0002-5152-9839"
    },
    {
      "affs": [
        0
      ],
      "name": "Stephanie Lee",
      "orcid": "0009-0005-7519-3286"
    },
    {
      "affs": [
        0
      ],
      "name": "John Hsieh",
      "orcid": "0009-0008-5752-3634"
    },
    {
      "affs": [
        0
      ],
      "name": "Alena Zalutskaya",
      "orcid": "0009-0001-7779-1571"
    },
    {
      "affs": [
        14
      ],
      "name": "Xiuning Le",
      "orcid": "0000-0002-8554-1185"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f7ycvepwpwnfy.bib",
  "cited_by": 0,
  "doi": "10.1158/1535-7163.mct-25-1056",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13728808/",
  "id": "f7ycvepwpwnfy",
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  "language": "en",
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  "native_subjects": [
    [
      "heading",
      "Animal Models of Cancer"
    ],
    [
      "heading",
      "Clinical Trial Results"
    ],
    [
      "heading",
      "Kinase Inhibitors"
    ],
    [
      "heading",
      "Lung Cancer"
    ],
    [
      "heading",
      "Preclinical Models"
    ],
    [
      "heading",
      "Small Molecule Agents"
    ],
    [
      "heading",
      "Small Molecule Therapeutics"
    ],
    [
      "openalex",
      "2740|Lung Cancer Treatments and Mutations"
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  "pdf_url": "https://aacrjournals.org/mct/article-pdf/doi/10.1158/1535-7163.MCT-25-1056/3793792/mct-25-1056.pdf",
  "pmcid": "PMC13728808",
  "pmid": "42126003",
  "published": "2026-05-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f7ycvepwpwnfy.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:21:43Z",
      "native_id": "PMC13728808",
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      "url": "https://doi.org/10.1158/1535-7163.mct-25-1056"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Lung Cancer Treatments and Mutations",
      "subfield": "general"
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  ],
  "title": "BLU-451, a CNS-Active, Potent, and Selective Small-Molecule Inhibitor against Uncommon EGFR Mutations",
  "title_text": "BLU-451, a CNS-Active, Potent, and Selective Small-Molecule Inhibitor against Uncommon EGFR Mutations",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:43Z",
  "url": "https://research.draconitic.com/paper/f7ycvepwpwnfy",
  "venue": "Molecular Cancer Therapeutics",
  "versions": []
}