Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/d41573-024-00122-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Background: VG-3927 is a highly potent, selective, brain penetrant, oral small molecule TREM2 agonist that is currently under development for the treatment of Alzheimer's disease (AD). TREM2, a receptor expressed on microglia in the brain is critical to microglial function in health and in disease. Among microglia-associated AD risk genes, partial loss-of-function variants of TREM2 confer 2-3 fold increase in risk for developing AD, motivating efforts to identify pharmacological agonists targeting TREM2 as a therapeutic option.
View Article and Find Full Text PDFModular Photoswitchable Molecular Glues for Chemo-optogenetic Control of Protein Function in Living Cells.
Angew Chem Int Ed Engl
January 2025
Umeå Universitet: Umea Universitet, Department of Chemistry, Department of Chemistry, 90187, Umeå, SWEDEN.
Optogenetic systems using photosensitive proteins and chemically induced dimerization/proximity (CID/CIP) approaches enabled by chemical dimerizers (also termed molecular glues), are powerful tools to elucidate the dynamics of biological systems and to dissect complex biological regulatory networks. Here, we report a versatile chemo-optogenetic system using modular, photoswitchable molecular glues (sMGs) that can undergo repeated cycles of optical control to switch protein function on and off. We use molecular dynamics (MD) simulations to rationally design the sMGs and further expand their scope by incorporating different photoswitches, resulting in sMGs with customizable properties.
View Article and Find Full Text PDFClinically and orally compatible formulation-manufactured DDX5 (p68)-targeting molecular glue FL118 products exhibit low toxicity but high efficacy against human cancer.
J Pharm Anal
November 2024
Department of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, 14263, USA.
Image 1.
View Article and Find Full Text PDFMolecular glue degrader for tumor treatment.
Front Oncol
December 2024
Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
Targeted Protein Degradation (TPD) represented by Proteolysis-Targeting Chimeras (PROTAC) is the frontier field in the research and development of antitumor therapy, in which oral drug HP518 Receives FDA Proceed Authorization for its IND Application for Prostate Cancer Treatment. Recently, molecular glue, functioning via degradation of the target protein is emerging as a promising modality for the development of therapeutic agents, while exhibits greater advantages over PROTAC, including improved efficiency, resistance-free properties, and the capacity to selectively target "undruggable" proteins. This marks a revolutionary advancement in the landscape of small molecule drugs.
View Article and Find Full Text PDFRoutes to molecular glue degrader discovery.
Trends Biochem Sci
January 2025
School of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China. Electronic address:
Molecular glue degraders (MGDs) represent a unique class of targeted protein degradation (TPD) modalities. By facilitating protein-protein interactions between E3 ubiquitin ligases and neo-substrates, MGDs offer a novel approach to target previously undruggable or insufficiently drugged disease-causing proteins. Here, we present an overview of recently reported MGDs, highlighting their diverse mechanisms, and we discuss mechanism-based strategies to discover new MGDs and neo-substrates.
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!