ArticleJournal of medicinal chemistry2018
Piperidinyl Ureas Chemically Control Defective in Cullin Neddylation 1 (DCN1)-Mediated Cullin Neddylation.
Article in Journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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
19 citing papers in PubMed, 42 citations in OpenAlex.
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- Which halogen to choose? Comparing the effects of chlorine and fluorine as bioisosteric substituents in drug design.Chemical science · 2026Review
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- Progression on Mechanism and Therapeutic Implications of Neddylation in Lung Cancer.Oncology research · 2026Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- Review
- Targeting neddylation as a novel approach to lung cancer treatment (Review).International journal of oncology · 2023Review
- NEDD8-conjugating enzyme E2s: critical targets for cancer therapy.Cell death discovery · 2023Review
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- A review on cullin neddylation and strategies to identify its inhibitors for cancer therapy.3 Biotech · 2022Article
- The Next Frontier: Translational Development of Ubiquitination, SUMOylation, and NEDDylation in Cancer.International journal of molecular sciences · 2022Review
- Improvement of Oral Bioavailability of Pyrazolo-Pyridone Inhibitors of the Interaction of DCN1/2 and UBE2M.Journal of medicinal chemistry · 2021Article
- Selective inhibition of cullin 3 neddylation through covalent targeting DCN1 protects mice from acetaminophen-induced liver toxicity.Nature communications · 2021Article
- Targeting neddylation E2s: a novel therapeutic strategy in cancer.Journal of hematology & oncology · 2021Review
- [Targeting Cullin-RING E3 ligases for anti-cancer therapy: efforts on drug discovery].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2020Review
- Anticancer drug discovery by targeting cullin neddylation.Acta pharmaceutica Sinica. B · 2020Review
- Discovery of Novel Pyrazolo-pyridone DCN1 Inhibitors Controlling Cullin Neddylation.Journal of medicinal chemistry · 2019Article
- Discovery of an Orally Bioavailable Inhibitor of Defective in Cullin Neddylation 1 (DCN1)-Mediated Cullin Neddylation.Journal of medicinal chemistry · 2018Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
We previously discovered and validated a class of piperidinyl ureas that regulate defective in cullin neddylation 1 (DCN1)-dependent neddylation of cullins. Here, we report preliminary structure-activity relationship studies aimed at advancing our high-throughput screen hit into a tractable tool compound for dissecting the effects of acute DCN1-UBE2M inhibition on the NEDD8/cullin pathway. Structure-enabled optimization led to a 100-fold increase in biochemical potency and modestly increased solubility and permeability as compared to our initial hit. The optimized compounds inhibit the DCN1-UBE2M protein-protein interaction in our TR-FRET binding assay and inhibit cullin neddylation in our pulse-chase NEDD8 transfer assay. The optimized compounds bind to DCN1 and selectively reduce steady-state levels of neddylated CUL1 and CUL3 in a squamous cell carcinoma cell line. Ultimately, we anticipate that these studies will identify early lead compounds for clinical development for the treatment of lung squamous cell carcinomas and other cancers.
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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.