ArticleCell death & disease2023
Vemurafenib inhibits necroptosis in normal and pathological conditions as a RIPK1 antagonist.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Necroptosis-related diseases are regulated by the unfolded protein response during endoplasmic reticulum stress.Genes & diseases · 2027Review
- Article
- Targeting the polyene chain represents an adjuvant strategy for optimizing polyene antifungals.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeting PANoptosis in atherosclerosis: bridging cell death mechanisms and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Antibody-lectin chimeras for glyco-immune checkpoint blockade.Nature biotechnology · 2025Article
- Screening of an FDA-Approved Drug Library: Menadione Induces Multiple Forms of Programmed Cell Death in Colorectal Cancer Cells via MAPK8 Cascades.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Integrative analysis of signaling and metabolic pathways, immune infiltration patterns, and machine learning-based diagnostic model construction in major depressive disorder.Scientific reports · 2025Article
- Acute lung injury: a view from the perspective of necroptosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- The regulated cell death at the maternal-fetal interface: beneficial or detrimental?Cell death discovery · 2024Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Necroptosis, a programmed cell death with necrotic-like morphology, has been recognized as an important driver in various inflammatory diseases. Inhibition of necroptosis has shown potential promise in the therapy of multiple human diseases. However, very few necroptosis inhibitors are available for clinical use as yet. Here, we identified an FDA-approved anti-cancer drug, Vemurafenib, as a potent inhibitor of necroptosis. Through direct binding, Vemurafenib blocked the kinase activity of receptor-interacting protein kinases 1 (RIPK1), impeded the downstream signaling and necrosome complex assembly, and inhibited necroptosis. Compared with Necrostain-1, Vemurafenib stabilized RIPK1 in an inactive DLG-out conformation by occupying a distinct allosteric hydrophobic pocket. Furthermore, pretreatment with Vemurafenib provided strong protection against necroptosis-associated diseases in vivo. Altogether, our results demonstrate that Vemurafenib is an effective RIPK1 antagonist and provide rationale and preclinical evidence for the potential application of approved drug in necroptosis-related diseases.
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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 Socratic graph.