ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
A Natural Small Molecule Mitigates Kidney Fibrosis by Targeting Cdc42-mediated GSK-3β/β-catenin Signaling.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 26 citations in OpenAlex.
- Direct pharmacological targeting of RAC1 by chlorogenic acid: A novel therapeutic approach for mesangial proliferative glomerulonephritis.Acta pharmaceutica Sinica. B · 2026Article
- Nicotinamide Mononucleotide Ameliorates Myocardial Fibrosis in Diabetic Mice Possibly by Modulating SIRT3 to Deacetylate GSK3β and Thereby Reducing the Phosphorylation of Smad3.Journal of cardiovascular translational research · 2026Article
- Herbacetin as a novel therapeutic agent for pulmonary and renal fibrosis by targeting TGFBR2 for degradation.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Fumarate-induced succination of A-kinase anchor protein 12 exacerbates renal inflammation and fibrosis.The Journal of clinical investigation · 2026Article
- Innovative strategies for anti-fibrotic drugs discovery from traditional Chinese medicine.Chinese herbal medicines · 2026Review
- Paeoniflorin inhibits colorectal cancer stem cell properties via regulating LINC01711/KMT2D/KLF7 axis.Journal of gastrointestinal oncology · 2026Article
- Isovitexin Alleviates Myocardial Ischemia by Targeting SLC25A4 and Modulating the AMPK/PGC-1International journal of molecular sciences · 2026Article
- Environmental Enrofloxacin Exposure as a Modifiable Driver of Mitochondria-Mediated Intestinal Aging and Barrier Dysfunction.Aging cell · 2026Article
- Small molecules targeting regulated cell death for chronic kidney disease therapy.Journal of pharmaceutical analysis · 2026Review
- Galangin-loaded biomimetic dendritic cells membrane nanovaccine reprograms the ovarian cancer microenvironmentMaterials today. Bio · 2026Article
- Chrysogenones A-E: Malonyl-Modified Ergosterone Derivatives from Deep-Sea-DerivedMarine drugs · 2026Article
- 7-Ketolithocholic Acid Exerts Anti-Renal Fibrotic Effects Through FXR-Mediated Inhibition of TGF-β/Smad and Wnt/β-Catenin Pathways.Pharmaceuticals (Basel, Switzerland) · 2025Article
- HIF-1α modulates β-catenin pathway to enhance the survival and angiogenesis of PBMSCs under hypoxia environment.World journal of stem cells · 2025Article
- Glycogen Synthase Kinase 3 Is Essential for Intestinal Cell Niche and Digestive Function.Biology · 2025Article
- Novel Evolutionarily Conserved Oncogene COA4 is Driven by KRAS Mutant and Promotes Cancer Metastasis Through Dual Mitochondrial Metabolism-Dependent and -Independent Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- UBC9-associated SUMOylation contributes to β-catenin activation and kidney fibrosis.Kidney international · 2025Article
- Development of a prognostic prediction signature for idiopathic pulmonary fibrosis by integrating multiple programmed cell death-related genes and machine learning algorithms.Journal of thoracic disease · 2025Article
- Target discovery-directed pharmacological mechanism elucidation of bioactive natural products.Medical review (2021) · 2025Review
- Cardiorenal syndrome: clinical diagnosis, molecular mechanisms and therapeutic strategies.Acta pharmacologica Sinica · 2025Review
- Inhibition of Rho GEFs attenuates pulmonary fibrosis through suppressing myofibroblast activation and reprogramming profibrotic macrophages.Cell death & disease · 2025Article
Corrections and comments
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Authors and funding
27 authors at 2 institutions in 2 countries.
Funding
Abstract
Kidney fibrosis is a common fate of chronic kidney diseases (CKDs), eventually leading to renal dysfunction. Yet, no effective treatment for this pathological process has been achieved. During the bioassay-guided chemical investigation of the medicinal plant Wikstroemia chamaedaphne, a daphne diterpenoid, daphnepedunin A (DA), is characterized as a promising anti-renal fibrotic lead. DA shows significant anti-kidney fibrosis effects in cultured renal fibroblasts and unilateral ureteral obstructed mice, being more potent than the clinical trial drug pirfenidone. Leveraging the thermal proteome profiling strategy, cell division cycle 42 (Cdc42) is identified as the direct target of DA. Mechanistically, DA targets to reduce Cdc42 activity and down-regulates its downstream phospho-protein kinase Cζ(p-PKCζ)/phospho-glycogen synthase kinase-3β (p-GSK-3β), thereby promoting β-catenin Ser33/37/Thr41 phosphorylation and ubiquitin-dependent proteolysis to block classical pro-fibrotic β-catenin signaling. These findings suggest that Cdc42 is a promising therapeutic target for kidney fibrosis, and highlight DA as a potent Cdc42 inhibitor for combating CKDs.
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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.