ArticleSignal transduction and targeted therapy2023
Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1.
Article in Signal transduction and targeted therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 153 citations in OpenAlex.
- Celastrol Attenuates Doxorubicin-Induced Heart Failure by Preserving Mitochondrial Integrity and Suppressing Oxidative Stress and Is Accompanied by Changes in Gut Microbiota.Pharmaceuticals (Basel, Switzerland) · 2026Article
- 3-Hydroxydehydroleucodin ameliorates neuroinflammation and ischemic brain injury by blocking the TRIM21-PRDX1 interaction.Acta pharmacologica Sinica · 2026Article
- The analgesic effect and mechanism of celastrol in formalin-induced inflammatory pain mouse model.Molecular and cellular biochemistry · 2026Article
- Chrysosplenetin-induced TMED3 aggregation triggers unfolded protein response in pancreatic cancer.EMBO molecular medicine · 2026Article
- Celastrol attenuates synovial inflammation and experimental arthritis by modulating PTGS2-associated ferroptosis resistance in fibroblast-like synoviocytes.Journal of molecular histology · 2026Article
- Design and evaluation of peroxiredoxin 1 agonist based on scaffold hopping of salvianolic acids and combinatorial click chemistry.Acta pharmacologica Sinica · 2026Article
- Cel-LDH dual-functional nanotherapy simultaneously promotes microglial efferocytosis and alleviates neuronal apoptosis for spinal cord injury recovery.Journal of nanobiotechnology · 2026Article
- Celastrol induces apoptosis of myelodysplastic syndrome cells through a ROS-dependent pro-apoptotic endoplasmic-reticulum stress pathway.Cancer cell international · 2026Article
- Review
- Exploring bacterial cytochrome P450s for selective activation of aliphatic C-H bonds in pentacyclic triterpenoids.Nature chemistry · 2026Article
- Article
- IL-3 Modulates Microglia Polarization and Attenuates Neuroinflammation in Traumatic Brain Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The YY1-KIF15-PRDX1 axis promotes gastric cancer progression by inducing mitochondrial ROS imbalance.Oncogene · 2026Article
- Self-assembling RADA16-I peptide in situ hydrogel loaded with Celastrol boost immunogenic cell death in oral squamous cell carcinoma.Drug delivery and translational research · 2026Article
- The Antitumor Potential of Celastrol: Research Progress on Antitumor Mechanisms and Strategies for Toxicity Reduction with Efficacy Enhancement.Biomolecules · 2026Review
- Oral Celastrol Nanomedicine Targeting Intestinal Antigen-Presenting Cells to Effectively Mitigate Autoimmune Uveitis via Gut-Retina Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Reinforced immunotherapy of M1 macrophage-derived exosomes with CEL on TNBC via regulating macrophage functions.Journal of advanced research · 2026Article
- Label-Free Target Discovery Strategy for Natural Active Products.Biomolecules · 2026Review
- Ginsenoside Rg5 Targets PRDX1 to Disrupt Redox Homeostasis and Induce Mitochondria-Dependent Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells.Molecules (Basel, Switzerland) · 2026Article
- Halorotetin B, A Novel Terpenoid Compound Derived from Marine Ascidian, Suppresses Tumor Growth by Targeting the Cell Cycle Regulator UBE2C.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a terpenoids natural product isolated from the plant Thunder God Vine, Celastrol is widely studied for its pharmacological activities, including anti-tumor activities. The clinical application of Celastrol is strictly limited due to its severe side effects, whereas previously revealed targets and mechanism of Celastrol seldom reduce its in vivo toxicity via structural optimization. Target identification has a far-reaching influence on the development of innovative drugs, and omics data has been widely used for unbiased target prediction. However, it is difficult to enrich target of specific phenotype from thousands of genes or proteins, especially for natural products with broad promising activities. Here, we developed a text-mining-based web-server tool to enrich targets from omics data of inquired compounds. Then peroxiredoxin 1 (PRDX1) was identified as the ROS-manipulating target protein of Celastrol in colorectal cancer. Our solved high-resolution crystal structure revealed the unique covalent binding mode of Celastrol with PRDX1. New derivative compound 19-048 with improved potency against PRDX1 and selectivity towards PRDX2~PRDX6 were synthesized based on crystal structure analysis. Both Celastrol and 19-048 effectively suppressed the proliferation of colorectal cancer cells. The anti-tumor efficacy of Celastrol and 19-048 was significantly diminished on xenograft nude mice bearing PRDX1 knock-down colorectal cancer cells. Several downstream genes of p53 signaling pathway were dramatically up-regulated with Celastrol or 19-048 treatment. Our findings reveal that the side effects of Celastrol could be reduced via structural modification, and PRDX1 inhibition is promising for the treatment of colorectal cancer.
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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.