{
  "abstract": "MCL-1 is the most widely expressed and most rapidly turned over pro-survival member of the BCL-2 family, and the survival of acute myeloid leukemia, multiple myeloma, and many solid tumors depends at least in part on this protein. Several MCL-1-selective inhibitors have entered clinical trials; however, because cardiomyocytes also depend on MCL-1 for survival, direct inhibition has a structurally narrow therapeutic window, single-agent activity has been modest, and no inhibitor has been approved to date. In recent years, the research focus of MCL-1 targeting has shifted from direct occupancy toward downregulation and degradation. CDK9/BET transcriptional inhibition, translational and signaling interventions, pro-ubiquitination, and PROTACs and molecular glues lower MCL-1 within hours and reverse venetoclax resistance, although no degrader has yet entered a registered trial. At present, MCL-1 intervention is positioned mainly as a combination and sequencing component in resistant disease; response prediction relies on dynamic BH3 profiling, and cardiac safety monitoring is a common prerequisite across all routes. Looking forward, the first clinical validation of the degradation paradigm and biomarker-driven patient selection will determine the clinical prospects of this target.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Review",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "Shuai Liu"
    },
    {
      "name": "Shan Jiang"
    },
    {
      "name": "Mengjiao Zhang"
    },
    {
      "name": "Weixiao Wang"
    },
    {
      "name": "Huiru Peng"
    },
    {
      "name": "Wei Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fzsqy83vs2657.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.2010618",
  "fulltext_url": null,
  "id": "fzsqy83vs2657",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.2010618",
  "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": [
    [
      "feed-journal",
      "medicine/pharmacology-toxicology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/fzsqy83vs2657.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:20:47Z",
      "native_id": "10.3389/fphar.2026.2010618",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.2010618"
    },
    {
      "first_seen": "2026-11-06T12:21:21Z",
      "native_id": "10.3389/fphar.2026.2010618",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.2010618/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/pharmacology-toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "From direct inhibition to induced degradation: clinical progress of MCL-1-targeted interventions in cancer",
  "title_text": "From direct inhibition to induced degradation: clinical progress of MCL-1-targeted interventions in cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T00:23:04Z",
  "url": "https://research.draconitic.com/paper/fzsqy83vs2657",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}