AI Article Synopsis
- The study introduces a new class of compounds based on a 2-benzyl hexanoic acid scaffold that function as dual modulators for γ-secretase and PPARγ.
- The research highlights the synthesis and modification of these compounds, with a focus on achieving better pharmacological activity and selectivity against unwanted targets.
- Specifically, Compound 17 demonstrates significant effectiveness with an IC(50) of 2.4 μM for Aβ42 and an EC(50) of 7.2 μM for PPARγ, indicating its potential for further testing in Alzheimer’s disease models.
Article Abstract
A novel set of dual γ-secretase/PPARγ modulators characterized by a 2-benzyl hexanoic acid scaffold is presented. Synthetic efforts were focused on the variation of the substitution pattern of the central benzene. Finally, we obtained a new class of 2,5-disubstituted 2-benzylidene hexanoic acid derivatives, which act as dual γ-secretase/PPARγ modulators in the low micromolar range. We have explored broad SAR and successfully improved the dual pharmacological activity and the selectivity profile against potential off-targets such as NOTCH and COX. Compound 17 showed an IC(50) Aβ42=2.4 μM and an EC(50) PPARγ=7.2 μM and could be a valuable tool to further evaluate the concept of dual γ-secretase/PPARγ modulators in animal models of Alzheimer's disease.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmc.2011.08.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Distinguishing abiotic corrosion from two types of microbiologically influenced corrosion (MIC) using a new electrochemical biofilm/MIC test kit.
J Environ Manage
January 2025
Department of Chemical & Biomolecular Engineering, Institute for Corrosion and Multiphase Technology, Ohio University, Athens, 45701, USA; Department of Biological Sciences, Molecular & Cellular Biology Program, Ohio University, Athens, OH, 45701, USA. Electronic address:
Biofilms can cause biofouling, water quality deterioration, and transmission of infectious diseases. They are also responsible for microbiologically influenced corrosion (MIC) which can cause leaks, resulting in environmental disasters. A new disposable biofilm/MIC test kit was demonstrated to distinguish abiotic corrosion of carbon steel from MIC.
View Article and Find Full Text PDFAutomated Classification of Cardiac Arrhythmia using Short-Duration ECG Signals and Machine Learning.
Biomed Phys Eng Express
January 2025
Electronics and Communication Engineering, Rajiv Gandhi University, Rono Hills, Doimukh, ITANAGAR, Itanagar, Arunachal Pradesh, 791112, INDIA.
Accurate detection of cardiac arrhythmias is crucial for preventing premature deaths. The current study employs a dual-stage Discrete Wavelet Transform (DWT) and a median filter to eliminate noise from ECG signals. Subsequently, ECG signals are segmented, and QRS regions are extracted for further preprocessing.
View Article and Find Full Text PDFChimeric Antigen Receptor-T Cells in Colorectal Cancer: Pioneering New Avenues in Solid Tumor Immunotherapy.
J Clin Oncol
January 2025
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Colorectal cancer (CRC) remains a major global health burden, being one of the most prevalent cancers with high mortality rates. Despite advances in conventional treatment modalities, patients with metastatic CRC often face limited options and poor outcomes. Chimeric antigen receptor-T (CAR-T) cell therapy, initially successful in hematologic malignancies, presents a promising avenue for treating solid tumors, including CRC.
View Article and Find Full Text PDFEngineered Microneedle System Enables the Smart Regulation of Nanodynamic Sterilization and Tissue Regeneration for Wound Management.
Adv Sci (Weinh)
January 2025
Department of Laboratory Medicine, School of Chemical Science and Engineering, Shanghai Tenth People's Hospital of Tongji University, Tongji University, Shanghai, 200092, P. R. China.
The healing of bacterial biofilm-infected wounds is a complex process, and the construction of emerging therapeutic modalities that regulate the microenvironment to magnify therapeutic effects and reduce biotoxicity is still highly challenging. Herein, an engineered microneedle (MN) patch is reported to mediate the efficient delivery of black phosphorus nanosheets (BP NSs) and copper peroxide nanodots (CP NDs) for dual nanodynamic sterilization and methicillin-resistant staphylococcus aureus (MRSA)-infected wound healing. Results demonstrate that the system can eliminate biofilm, reduce cytotoxicity, promote angiogenesis and tissue regeneration by the multiple advantages of chemodynamic therapy (CDT), enhanced photodynamic therapy (PDT), and improved degradation process from BP NSs to phosphate for promoting cell proliferation.
View Article and Find Full Text PDFIdentification of novel PfEMP1 variants containing domain cassettes 11, 15 and 8 that mediate the Plasmodium falciparum virulence-associated rosetting phenotype.
PLoS Pathog
January 2025
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a diverse family of variant surface antigens, encoded by var genes, that mediates binding of infected erythrocytes to human cells and plays a key role in parasite immune evasion and malaria pathology. The increased availability of parasite genome sequence data has revolutionised the study of PfEMP1 diversity across multiple P. falciparum isolates.
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!