ArticleScientific reports2015
Selective targeting of PPARγ by the natural product chelerythrine with a unique binding mode and improved antidiabetic potency.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 57 citations in OpenAlex.
- Distinctive Behavior and Selective Modulation of PPARγ by Pentacyclic Triterpenoid Pomolic Acid and Hederagenin fromJournal of agricultural and food chemistry · 2026Article
- Review
- Biotechnological Advances in Sanguinarine and Chelerythrine Production from Plume Poppy (Plants (Basel, Switzerland) · 2025Review
- Unraveling PPARβ/δ nuclear receptor agonistsRSC advances · 2025Article
- Natural products targeting inflammation-related metabolic disorders: A comprehensive review.Heliyon · 2023Review
- Exploring the shared molecular mechanism of microvascular and macrovascular complications in diabetes: Seeking the hub of circulatory system injury.Frontiers in endocrinology · 2023Article
- Antiaging effects of dietary supplements and natural products.Frontiers in pharmacology · 2023Review
- Article
- Impact of Phytochemicals on PPAR Receptors: Implications for Disease Treatments.PPAR research · 2022Review
- Rediscovery of Traditional Plant Medicine: An Underestimated Anticancer Drug of Chelerythrine.Frontiers in pharmacology · 2022Review
- Integrating network pharmacology and experimental validation to clarify the anti-hyperuricemia mechanism of cortex phellodendri in mice.Frontiers in pharmacology · 2022Article
- Qihuang Zhuyu Formula Attenuates Atherosclerosis via Targeting PPAROxidative medicine and cellular longevity · 2022Article
- Chelerythrine suppresses proliferation and metastasis of human prostate cancer cells via modulating MMP/TIMP/NF-κB system.Molecular and cellular biochemistry · 2020Article
- The PPARPPAR research · 2020Review
- PPARγ S273 Phosphorylation Modifies the Dynamics of Coregulator Proteins Recruitment.Frontiers in endocrinology · 2020Article
- Chelerythrine induces apoptosis via ROS-mediated endoplasmic reticulum stress and STAT3 pathways in human renal cell carcinoma.Journal of cellular and molecular medicine · 2020Article
- CMHX008, a PPARγ partial agonist, enhances insulin sensitivity with minor influences on bone loss.Genes & diseases · 2018Article
- Functional Regulation of PPARs through Post-Translational Modifications.International journal of molecular sciences · 2018Review
- Chelerythrine induced cell death through ROS-dependent ER stress in human prostate cancer cells.OncoTargets and therapy · 2018Article
- Induction of reactive oxygen species-stimulated distinctive autophagy by chelerythrine in non-small cell lung cancer cells.Redox biology · 2017Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 2 diabetes mellitus (T2DM) is a pervasive metabolic syndrome that is characterized by insulin resistance, hyperglycemia and dyslipidemia. As full agonists of PPARγ, thiazolidinedione (TZD) drugs elicit antidiabetic effects by targeting PPARγ but is accompanied by weight gain, fluid retention and cardiovascular risk associated with their transcriptional agonism potency. We here identify a natural product chelerythrine as a unique selective PPAR modulator (SPPARM) with a potent PPARγ binding activity but much less classical receptor transcriptional agonism. Structural analysis reveals that chelerythrine exhibits unique binding in parallel with H3 of PPARγ. Unlike TZDs, chelerythrine destabilizes helix 12, especially residue tyrosine 473, resulting in a loose configuration of AF-2 and a selective cofactor profile distinct from TZDs, leading to a differential target gene profile in adipogenesis in db/db diabetic mice. Moreover, chelerythrine improved insulin sensitivity by more potently blocking the phosphorylation of PPARγ by CDK5 compared to TZDs. These data fundamentally elucidate the mechanism by which chelerythrine retains the benefits of improving insulin sensitivity while reducing the adverse effects of TZDs, suggesting that the natural product chelerythrine is a very promising pharmacological agent by selectively targeting PPARγ for further development in the clinical treatment of insulin resistance.
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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.