ArticleACS chemical biology2017
Targeting NF-κB p65 with a Helenalin Inspired Bis-electrophile.
Article in ACS chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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
17 citing papers in PubMed, 34 citations in OpenAlex.
- Structural Modification of Sesquiterpene Lactones via Michael Addition: Improved Bioactivity and Pharmacokinetics.International journal of molecular sciences · 2026Review
- Helenalin: a multifaceted sesquiterpene lactone with diverse biological activities-an integrative pharmacological and computational evidence.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Dimers of isatin derived α-methylene-γ-butyrolactone as potent anti-cancer agents.Bioorganic & medicinal chemistry letters · 2022Article
- Stapling proteins in the RELA complex inhibits TNFα-induced nuclear translocation of RELA.RSC chemical biology · 2022Article
- Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones.Biomedicines · 2021Review
- Identification of a Covalent Importin-5 Inhibitor, Goyazensolide, from a Collective Synthesis of Furanoheliangolides.ACS central science · 2021Article
- Helenalin Facilitates Reactive Oxygen Species-Mediated Apoptosis and Cell Cycle Arrest by Targeting Thioredoxin Reductase-1 in Human Prostate Cancer Cells.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Function-Oriented and Modular (+/-)-cis-Pseudoguaianolide Synthesis: Discovery of New Nrf2 Activators and NF-κB Inhibitors.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Synthesis of Guaianolide Analogues with a Tunable α-Methylene-γ-lactam Electrophile and Correlating Bioactivity with Thiol Reactivity.Journal of medicinal chemistry · 2020Article
- The potential role of sesquiterpene lactones isolated from medicinal plants in the treatment of the metabolic syndrome - A review.South African journal of botany : official journal of the South African Association of Botanists = Suid-Afrikaanse tydskrif vir plantkunde : amptelike tydskrif van die Suid-Afrikaanse Genootskap van Plantkundiges · 2020Review
- Identification of a Selective RelA Inhibitor Based on DSE-FRET Screening Methods.International journal of molecular sciences · 2020Article
- Stabilization of the histone acetyltransferase Tip60 by deubiquitinating enzyme USP7 stimulates the release of pro-inflammatory mediators in acute lung injury.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Dectin-1 Facilitates IL-18 Production for the Generation of Protective Antibodies AgainstFrontiers in microbiology · 2020Article
- Helenalin Analogues Targeting NF-κB p65: Thiol Reactivity and Cellular Potency Studies of Varied Electrophiles.ChemMedChem · 2018Article
- Budlein A, a Sesquiterpene Lactone FromFrontiers in pharmacology · 2018Article
- The Sesquiterpene Lactone, Budlein A, Inhibits Antigen-Induced Arthritis in Mice: Role of NF-κB and Cytokines.Inflammation · 2017Article
- Semisynthesis, an Anti-Inflammatory Effect of Derivatives of 1β-Hydroxy Alantolactone from Inula britannica.Molecules (Basel, Switzerland) · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The canonical NF-κB signaling pathway is a mediator of the cellular inflammatory response and a target for developing therapeutics for multiple human diseases. The furthest downstream proteins in the pathway, the p50/p65 transcription factor heterodimer, have been recalcitrant toward small molecule inhibition despite the substantial number of compounds known to inhibit upstream proteins in the activation pathway. Given the roles of many of these upstream proteins in multiple biochemical pathways, targeting the p50/p65 heterodimer offers an opportunity for enhanced on-target specificity. Toward this end, the p65 protein presents two nondisulfide cysteines, Cys38 and Cys120, at its DNA-binding interface that are amenable to targeting by covalent molecules. The natural product helenalin, a sesquiterpene lactone, has been previously shown to target Cys38 on p65 and ablate its DNA-binding ability. Using helenalin as inspiration, simplified helenalin analogues were designed, synthesized, and shown to inhibit induced canonical NF-κB signaling in cell culture. Moreover, two simplified helenalin probes were proficient at forming covalent protein adducts, binding to Cys38 on recombinant p65, and targeting p65 in HeLa cells without engaging canonical NF-κB signaling proteins IκBα, p50, and IKKα/β. These studies further support that targeting the p65 transcription factor-DNA interface with covalent small molecule inhibitors is a viable approach toward regulating canonical NF-κB signaling.
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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.