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Drug Development.
Alzheimers Dement
December 2024
University of Florida / Center for Translational Research in Neurodegenerative Disease, Gainesville, FL, USA.
Background: Vaxxinity is developing an active immunotherapy targeting Tau for Alzheimer's disease (AD) and other tauopathies. VXX-301 is a multi-epitope vaccine designed to target the N-terminal and repeat domains of Tau. This design enables targeting multiple forms of Tau thought to contribute to Tau associated pathologies.
View Article and Find Full Text PDFBisubstrate Analog Inhibitors of DXP Synthase Show Species Specificity.
Biochemistry
January 2025
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.
1-Deoxy-d-xylulose 5-phosphate synthase (DXPS) is a unique thiamin diphosphate (ThDP)-dependent enzyme that catalyzes the formation of DXP, a branchpoint metabolite required for the biosynthesis of vitamins and isoprenoids in bacterial pathogens. DXPS has relaxed substrate specificity and utilizes a gated mechanism, equipping DXPS to sense and respond to diverse substrates. We speculate that pathogens utilize this distinct gated mechanism in different ways to support metabolic adaptation during infection.
View Article and Find Full Text PDFDesign, synthesis, and biological evaluation of novel FGFR1 PROTACs.
Bioorg Chem
December 2024
Jiangsu Key Laboratory of Drug Design & Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address:
Dysregulation of the fibroblast growth factor receptor 1 (FGFR1) signaling has prompted efforts to develop therapeutic agents, which is a carcinogenic driver of many cancers, including breast, prostate, bladder, and chronic myeloid leukemia. Despite significant progress in the development of potent and selective FGFR inhibitors, the long-term efficacy of these drugs in cancer therapy has been hampered by the rapid onset of acquired resistance. Therefore, more drug discovery strategies are needed to promote the development of FGFR-targeted drugs.
View Article and Find Full Text PDFKDM6A facilitates Xist upregulation at the onset of X inactivation.
Biol Sex Differ
January 2025
Department of Laboratory Medicine and Pathology, School of Medicine, University of Washington, Seattle, WA, 98195, USA.
Background: X chromosome inactivation (XCI) is a female-specific process in which one X chromosome is silenced to balance X-linked gene expression between the sexes. XCI is initiated in early development by upregulation of the lncRNA Xist on the future inactive X (Xi). A subset of X-linked genes escape silencing and thus have higher expression in females, suggesting female-specific functions.
View Article and Find Full Text PDFAssociation of higher potency statin use with risk of osteoporosis and fractures in patients with stroke in a Korean nationwide cohort study.
Sci Rep
December 2024
School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, 16419, Gyeonggi-do, South Korea.
This population-based cohort study aimed to evaluate the risk of osteoporosis and fractures associated with higher-potency statin use compared to lower-potency statin use in patients with stroke, using data from the Health Insurance and Review Assessment database of South Korea (2010-2019). Patients who received statin within 30 days after hospitalization for a new-onset stroke (n = 276,911) were divided into higher-potency (n = 212,215, 76.6%) or lower-potency (n = 64,696, 23.
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