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FT-4202, a selective pyruvate kinase R activator for sickle cell disease.
Exp Hematol
January 2025
Forma Therapeutics, Inc., Watertown, MA.
Anemia in patients with sickle cell disease (SCD) increases 2,3-diphosphoglycerate (2,3-DPG), decreasing hemoglobin-oxygen (HbO) affinity to improve oxygen offloading and promote hemoglobin polymerization (sickling) of red blood cells (RBCs). We report the discovery of FT-4202, an investigational, selective pyruvate kinase type-R (PKR) activator with a multimodal mechanism of action and potential to increase ATP and decrease 2,3-DPG, resulting in increased HbO affinity, decreased Hb polymerization, and improved RBC health. FT-4202 was identified via structure-enabled lead optimization medicinal chemistry using X-ray crystallography, molecular modeling, and thermal shift assays.
View Article and Find Full Text PDFFeasibility of Pay for Performance and Transparency Interventions on the Selection and Quality of Observational Management for Patients with Low-Risk Prostate Cancer in the Community Practice.
Urol Pract
October 2024
Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Cardiovascular and Renal Effects Induced by Alpha-Lipoic Acid Treatment in Two-Kidney-One-Clip Hypertensive Rats.
Biomedicines
August 2024
Laboratory of Nutrition, Physical Activity and Phenotypic Plasticity, Federal University of Pernambuco-UFPE, Vitória de Santo Antão 55608-680, Brazil.
α-Lipoic acid (LA) is an antioxidant of endogenous production, also obtained exogenously. Oxidative stress is closely associated with hypertension, which causes kidney injury and endothelial dysfunction. Here, we evaluated the cardiovascular and renal effects of LA in the two-kidney-one-clip (2K1C) hypertension model.
View Article and Find Full Text PDFVirulence phenotypes differ between toxigenic Vibrio parahaemolyticus isolated from western coasts of Europe.
Microbiol Res
August 2024
Ifremer, Univ Brest, CNRS, IRD, LEMAR, Plouzané F-29280, France. Electronic address:
Vibrio parahaemolyticus is the leading bacterial cause of gastroenteritis associated with seafood consumption worldwide. Not all members of the species are thought to be pathogenic, thus identification of virulent organisms is essential to protect public health and the seafood industry. Correlations of human disease and known genetic markers (e.
View Article and Find Full Text PDFPublisher's Note: "Connecting microscopic and mesoscopic mechanics in model structural glasses" [J. Chem. Phys. 160, 094113 (2024)].
J Chem Phys
May 2024
CNRS, LIPhy, Univ. Grenoble Alpes, 38000 Grenoble, France and Navier, CNRS, Univ Gustave Eiffel, Marne-la-Vallée, France.
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