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Conformationally Restricted Macrocycles as Improved FKBP51 Inhibitors Enabled by Systematic Linker Derivatization.
Angew Chem Int Ed Engl
January 2025
Darmstadt University of Technology: Technische Universitat Darmstadt, Clemens-Schöpf-Institute of Organic Chemistry and Biochemistry, Alarich-Weiss-Strasse 4, 64287, Darmstadt, GERMANY.
Macrocycles are increasingly considered as promising modalities to target challenging intracellular proteins. However, strategies for transitioning from active linear starting points to improved macrocycles are still underdeveloped. Here we explored the derivatization of linkers as an approach for macrocycle optimization.
View Article and Find Full Text PDFIntergovernmental or fully independent? Designing a scientific panel on evidence for action against antimicrobial resistance.
PLOS Glob Public Health
January 2025
Global Strategy Lab, Dahdaleh Institute for Global Health Research, York University, Toronto, Ontario, Canada.
Effective global action against antimicrobial resistance (AMR) relies on the successful synthesis and translation of rigorous scientific evidence into policy and practice. Despite a call in 2019 by the Interagency Coordination Group on AMR to establish a policy-science interface, and the reaffirmation to establish a scientific panel in the 2024 Political Declaration on Antimicrobial Resistance, no authoritative entity currently exists that synthesizes the scientific evidence on AMR and outlines policy options based on the best scientific insight. A Scientific Panel on Evidence for Action against AMR (SPEA) could address this gap, as well as contribute to additional governance gaps in the space of AMR, by facilitating better global coordination and cooperation; establishing real-time evidence to guide policy actions; and monitoring progress towards any globally agreed upon AMR goals and targets.
View Article and Find Full Text PDFBackground And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe subtype, metabolic dysfunction-associated steatohepatitis (MASH), are highly prevalent and strongly associated with obesity and type 2 diabetes (T2D). This study sought to identify challenges to the diagnosis, treatment and management of people living with MASLD and MASH and understand the key barriers to adopting relevant clinical guidelines.
Methods: A real-world, cross-sectional study (BARRIERS-MASLD) consisting of a quantitative survey and qualitative interviews of physicians in France, Germany, Italy, Spain and the United Kingdom was conducted from March to September 2023.
Canine mammary tumors as a promising adjunct preclinical model for human breast cancer research: similarities, opportunities, and challenges.
Arch Pharm Res
January 2025
Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, 28644, Republic of Korea.
Despite significant progress in the field of human breast cancer research and treatment, there is a consistent increase in the incidence rate of 0.5 percent annually, posing challenges in the development of effective novel therapeutic strategies. The failure rate of drugs in clinical trials stands at approximately 95%, primarily attributed to the limitations and lack of reliability of existing preclinical models, such as mice, which do not mimic human tumor biology.
View Article and Find Full Text PDFWhile a new government may have brought changes in all sectors in 2024, the veterinary world had its own challenges and opportunities. From an investigation into the veterinary services market for pets to livestock diseases and governance reform, 2024 was far from quiet. Kathryn Clark reports.
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