ArticleImmunity2024
A RIPK1-specific PROTAC degrader achieves potent antitumor activity by enhancing immunogenic cell death.
Article in Immunity, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
58 citing papers in PubMed.
- Harnessing necroptosis via RIPK1 degradation to potentiate radio-immunotherapy in cervical cancer.Bioactive materials · 2027Article
- One adaptor, multiple outcomes: decoding TRIFosome heterogeneity.Biochemical Society transactions · 2026Review
- Programmed cell death in inflammation: interactions and holistic perspective.Cellular & molecular immunology · 2026Review
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- Reversible control of CAR T cells through PROTAC compound targeting bromodomain mutant.Molecular therapy. Oncology · 2026Article
- Discovery and Development of First-in-Class Cereblon-Recruiting RIPK1 Degraders.Journal of medicinal chemistry · 2026Article
- A multi-level charged micelle-based microneedle transdermal system for immunosuppressive tumor microenvironment regulation and synergistic therapy.Materials today. Bio · 2026Article
- PROTAC-mediated regulation of programmed cell death: From molecular mechanisms to therapeutic breakthroughs.Innovation (Cambridge (Mass.)) · 2026Review
- IL-18 derived from microwave-ablated osteosarcoma facilitates antitumor response.Journal for immunotherapy of cancer · 2026Article
- Toll-like Receptor 3 as a Context-Dependent Molecular Switch in Epithelial Cancers: Balancing Cell Death and Tumor-Supportive Programs.International journal of molecular sciences · 2026Review
- PRMT3-Mediated Arginine Methylation Stabilizes PCSK9 to Promote Aortic Valve Calcification.Circulation · 2026Article
- Metastable Protein-Protein Interactions as a Design Principle for PROTACs: Insights from the RIPK1-VHL System.JACS Au · 2026Article
- Discovery and Development of First-in-Class Cereblon-Recruiting RIPK1 Degraders.bioRxiv : the preprint server for biology · 2026Article
- Programmed cell death in cancer: targeting necroptosis to kill tumor cell.Cell death discovery · 2026Review
- Structural dynamics of the midnolin-proteasome during ubiquitin-independent substrate turnover.Nature communications · 2026Article
- RIPK1 as a potential target to augment DC efficacy in tumor immunotherapy.Cancer immunology, immunotherapy : CII · 2026Article
- CD8Nature communications · 2026Article
- Necroptosis in both tumour and stromal compartments determines responsiveness to immunogenic cell death-based immunotherapy.Nature communications · 2026Article
- Immune Aging as a Failure of Programmed Cell Death Coordination.International journal of molecular sciences · 2026Review
- Design, synthesis, and biological evaluation of RIPK1-targeting PROTACs.Molecular diversity · 2026Article
Corrections and comments
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Authors and funding
45 authors.
Funding
Abstract
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a critical stress sentinel that coordinates cell survival, inflammation, and immunogenic cell death (ICD). Although the catalytic function of RIPK1 is required to trigger cell death, its non-catalytic scaffold function mediates strong pro-survival signaling. Accordingly, cancer cells can hijack RIPK1 to block necroptosis and evade immune detection. We generated a small-molecule proteolysis-targeting chimera (PROTAC) that selectively degraded human and murine RIPK1. PROTAC-mediated depletion of RIPK1 deregulated TNFR1 and TLR3/4 signaling hubs, accentuating the output of NF-κB, MAPK, and IFN signaling. Additionally, RIPK1 degradation simultaneously promoted RIPK3 activation and necroptosis induction. We further demonstrated that RIPK1 degradation enhanced the immunostimulatory effects of radio- and immunotherapy by sensitizing cancer cells to treatment-induced TNF and interferons. This promoted ICD, antitumor immunity, and durable treatment responses. Consequently, targeting RIPK1 by PROTACs emerges as a promising approach to overcome radio- or immunotherapy resistance and enhance anticancer therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.