Type 2 diabetes is at epidemic proportions and thus development of novel pharmaceutical therapies for improving insulin sensitivity has become of paramount importance. The objectives of the current study were to develop novel dual PPARγ/δ agonists without the deleterious side effects associated with full PPARγ agonists. Docking simulations of 23 novel compounds within the ligand binding domain of PPARγ/δ were performed using AutoDock Vina which consistently reproduced experimental binding poses from known PPAR agonists. Comparisons were made and described with other docking programs AutoDock and Surflex-Dock (from SYBYL-X). Biological evaluation of compounds was accomplished by transcriptional promoter activity assays, quantitative PCR gene analysis for known PPARγ/δ targets as well as in vitro assays for lipid accumulation and mitochondrial biogenesis verses known PPAR agonists. We found one (compound 9) out of the 23 compounds evaluated, to be the most potent and selective dual PPARγ/δ agonist which did not display the deleterious side effects associated with full PPARγ agonists.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2012.11.060 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Global transcriptome profiling of ST09 treated breast cancer cells identifies miR-197-5p/GPX3 antioxidant axis as a regulator of tumorigenesis.
Int Immunopharmacol
January 2025
Institute of Bioinformatics and Applied Biotechnology, Electronic City Phase 1, Bangalore 560100 India. Electronic address:
ROS (Reactive Oxygen Species) has a dual role in tumorigenesis. Some cancers have high ROS conditions, and others have low ROS. TNBC thrives on high ROS compared to other Breast Cancer subtypes.
View Article and Find Full Text PDFDual-hybrid intrusion detection system to detect False Data Injection in smart grids.
PLoS One
January 2025
Department of Electrical Engineering, College of Engineering, Taif University, Taif, Saudi Arabia.
Modernizing power systems into smart grids has introduced numerous benefits, including enhanced efficiency, reliability, and integration of renewable energy sources. However, this advancement has also increased vulnerability to cyber threats, particularly False Data Injection Attacks (FDIAs). Traditional Intrusion Detection Systems (IDS) often fall short in identifying sophisticated FDIAs due to their reliance on predefined rules and signatures.
View Article and Find Full Text PDFProtein phosphatases are critical for regulating cell signaling, cell cycle, and cell fate decisions, and their dysregulation leads to an array of human diseases like cancer. The dual specificity phosphatases (DUSPs) have emerged as important factors driving tumorigenesis and cancer therapy resistance. DUSP12 is a poorly characterized atypical DUSP widely conserved throughout evolution.
View Article and Find Full Text PDFThe use of incretin analogues has emerged in recent years as an effective approach to achieve both enhanced insulin secretion and weight loss in type 2 diabetes (T2D) patients. Agonists which bind and stimulate multiple receptors have shown particular promise. However, off target effects, including nausea and diarrhoea, remain a complication of using these agents, and modified versions with optimized pharmacological profiles and/or biased signaling at the cognate receptors are increasingly sought.
View Article and Find Full Text PDFMETTL3/miR-192-5p/SCD1 Axis Regulates Lipid Metabolism to Affect T Cell Differentiation in Asthma.
Mediators Inflamm
January 2025
Department of Pediatric Pulmonology, Children's Hospital of Soochow University, No 303, Jingde Road, Suzhou 215003, China.
This study aimed to explore the mechanisms underlying T-cell differentiation in asthma. Flow cytometry was performed to detect Th cells. LC-MS/MS was performed to assess lipid metabolism.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!