ArticleCell discovery2021
Discovery of a cooperative mode of inhibiting RIPK1 kinase.
Article in Cell discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The trial behind it
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- PPP1R3G-RIPK1-ZBP1 axis activates early-stage apoptosis and late-stage necroptosis to promote doxorubicin-induced cardiotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- PANoptosis as a drug discovery framework: integrating cell death architecture with clinical translation.Genes and immunity · 2026Review
- Targeting PANoptosis in atherosclerosis: bridging cell death mechanisms and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Decoding protein dynamics with limited proteolysis coupled to mass spectrometry: A comprehensive review.Journal of pharmaceutical analysis · 2025Review
- FDA-approved phensuximide inhibits RIPK1-dependent immunogenic cell death.Cell death & disease · 2025Article
- Spermidine mediates acetylhypusination of RIPK1 to suppress diabetes onset and progression.Nature cell biology · 2024Article
- Structure-based development of potent and selective type-II kinase inhibitors of RIPK1.Acta pharmaceutica Sinica. B · 2024Article
- Die Hard: Necroptosis and its Impact on Age-Dependent Neuroinflammatory Diseases.Frontiers in cell death · 2024Article
- Ferroptosis: Underlying mechanism and the crosstalk with other modes of neuronal death after intracerebral hemorrhage.Frontiers in cellular neuroscience · 2023Review
- Integrative analysis reveals structural basis for transcription activation of Nurr1 and Nurr1-RXRα heterodimer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Do pyroptosis, apoptosis, and necroptosis (PANoptosis) exist in cerebral ischemia? Evidence from cell and rodent studies.Neural regeneration research · 2022Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
RIPK1, a death domain-containing kinase, has been recognized as an important therapeutic target for inhibiting apoptosis, necroptosis, and inflammation under pathological conditions. RIPK1 kinase inhibitors have been advanced into clinical studies for the treatment of various human diseases. One of the current bottlenecks in developing RIPK1 inhibitors is to discover new approaches to inhibit this kinase as only limited chemotypes have been developed. Here we describe Necrostatin-34 (Nec-34), a small molecule that inhibits RIPK1 kinase with a mechanism distinct from known RIPK1 inhibitors such as Nec-1s. Mechanistic studies suggest that Nec-34 stabilizes RIPK1 kinase in an inactive conformation by occupying a distinct binding pocket in the kinase domain. Furthermore, we show that Nec-34 series of compounds can synergize with Nec-1s to inhibit RIPK1 in vitro and in vivo. Thus, Nec-34 defines a new strategy to target RIPK1 kinase and provides a potential option of combinatorial therapy for RIPK1-mediated diseases.
Identifiers
What OpenQuestion holds
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.