ArticleNature chemical biology2019
Harnessing the anti-cancer natural product nimbolide for targeted protein degradation.
Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 198 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
198 citing papers in PubMed, 1 synthesis or guideline pooled it, 412 citations in OpenAlex.
- Cellular functions and molecular mechanisms of ubiquitination in osteosarcoma.Frontiers in oncology · 2022Pooled it
- Context matters in PROTAC design: navigating the trade-off between degradation and developability.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- PROTACs in personalized and precision medicine: transforming targeted therapy with advances in selectivity and patient stratification.Cancer chemotherapy and pharmacology · 2026Review
- Dual E3 ligase recruitment by monovalent degraders for tunable SMARCA 2/4 degradation.Nature chemical biology · 2026Article
- Unraveling the secrets of novel PROTACs to improve degradation efficacy.Molecular diversity · 2026Review
- Identification of Clofibric Acid as a Synoviolin (SYVN1) Ligand for Proteolysis-Targeting Chimera (PROTAC) Development.ACS medicinal chemistry letters · 2026Article
- Targeted protein degradation: bridging chemical biology and clinical translation.Acta pharmacologica Sinica · 2026Review
- Igalan attenuates sepsis-induced inflammation through covalent targeting of the NLRP3 inflammasome pathway.RSC chemical biology · 2026Article
- A Global Ligandability Map of Tryptoline Butynamide Stereoprobes Identifies Covalent Inhibitors of the Actin Maturation Protease.Journal of the American Chemical Society · 2026Article
- Review
- Progress and application of activity-based protein profiling for the discovery of natural product targets.Molecular diversity · 2026Review
- Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.ACS pharmacology & translational science · 2026Review
- Discovery of SKP2-Recruiting PROTACs for Target Protein Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Specificity and recognition of the ADP-ribosyl-ubiquitin modification in the DNA damage response.PLoS biology · 2026Article
- Small-molecule degraders for oncogenic KRASNature communications · 2026Article
- An Optimized RNF126-Targeting Covalent Handle for Molecular Glue Degraders.bioRxiv : the preprint server for biology · 2026Article
- A Global Ligandability Map of Tryptoline Butynamide Stereoprobes Identifies Covalent Inhibitors of the Actin Maturation Protease ACTMAP.bioRxiv : the preprint server for biology · 2026Article
- Proteolysis-targeting chimera (PROTAC) nanomedicines toward cancer treatment: From synthesis to therapeutic delivery.Biomaterials · 2026Review
- Deciphering the regulatory landscape of enhancer RNAs in health and disease.Signal transduction and targeted therapy · 2026Review
- Targeted Protein Degradation in Lung Cancer: The Emerging Role of PROTAC Technology and E3 Ligases.Current medicinal chemistry · 2026Review
138 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on byStick it to E3s.2019
Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
Nimbolide, a terpenoid natural product derived from the Neem tree, impairs cancer pathogenicity; however, the direct targets and mechanisms by which nimbolide exerts its effects are poorly understood. Here, we used activity-based protein profiling (ABPP) chemoproteomic platforms to discover that nimbolide reacts with a novel functional cysteine crucial for substrate recognition in the E3 ubiquitin ligase RNF114. Nimbolide impairs breast cancer cell proliferation in-part by disrupting RNF114-substrate recognition, leading to inhibition of ubiquitination and degradation of tumor suppressors such as p21, resulting in their rapid stabilization. We further demonstrate that nimbolide can be harnessed to recruit RNF114 as an E3 ligase in targeted protein degradation applications and show that synthetically simpler scaffolds are also capable of accessing this unique reactive site. Our study highlights the use of ABPP platforms in uncovering unique druggable modalities accessed by natural products for cancer therapy and targeted protein degradation applications.
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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.