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Repression of PFKFB3 sensitizes ovarian cancer to PARP inhibitors by impairing homologous recombination repair.
Cell Commun Signal
January 2025
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.
View Article and Find Full Text PDFInhibition of platelet activation process upon tris (2-chloroethyl) phosphate exposure: Role of PFKP-mediated glycolysis and the pentose phosphate pathway.
Environ Pollut
January 2025
Department of Occupational Health and Environmental Health, School of Public Health, Qingdao University, Qingdao, China.
Tris (2-chloroethyl) phosphate (TCEP), recognized as an emerging pollutant, has been frequently detected in human blood. Maintenance of blood homeostasis is indispensable for regulating various physiological states and overall health, yet hematological toxicology of TCEP has not been extensively investigated. Platelets, a vital component of blood, are fundamental in the processes of hemostasis and thrombosis through their activation; thus, this study was designed to elucidate the effects and underlying mechanisms of TCEP on platelet activation.
View Article and Find Full Text PDFERK-USP9X-coupled regulation of thymidine kinase 1 promotes both its enzyme activity-dependent and its enzyme activity-independent functions for tumor growth.
Nat Struct Mol Biol
January 2025
Zhejiang Provincial Key Laboratory of Pancreatic Disease, Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Thymidine kinase 1 (TK1), a crucial enzyme in DNA synthesis, is highly expressed in various cancers. However, the mechanisms underlying its elevated expression and the implications for tumor metabolism remain unclear. Here we demonstrate that activation of growth factor receptors enhances TK1 expression.
View Article and Find Full Text PDFPhenolic acids from Anisopus mannii modulates phosphofructokinase 1 to improve glycemic control in patients with type 2 diabetes: A double-blind, randomized, clinical trial.
Pharmacol Res
January 2025
Department of Biochemistry, Imo State University, Owerri, Nigeria.
Phenolic acid-rich fraction from Anisopus mannii (PhAM) contains abundance of ferulic acid, gallic acid, protocatechuic acid, and syringic acid. Among other glycolytic enzymes, in vitro, PhAM counteracted the binding of sodium orthovanadate to phosphofructokinase 1 (PFK-1), improving its activities. In a rat model of diet-induced diabetes, PhAM monotherapy reduced HbA1c by an average of 0.
View Article and Find Full Text PDFAsymmetric Synthesis, Structure Determination, and Biologic Evaluation of Isomers of TLAM as PFK1 Inhibitors.
ACS Med Chem Lett
January 2025
Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35 Yamate-cho, Suita, Osaka 564-8680, Japan.
Inhibiting phosphofructokinase-1 (PFK1) is a promising approach for treating lactic acidosis and mitochondrial dysfunction by activating oxidative phosphorylation. Tryptolinamide (TLAM) has been shown as a PFK1 inhibitor, but its complex stereochemistry, with 16 possible isomers complicates further development. We conducted an asymmetric synthesis, determined the absolute configurations, and evaluated the PFK1 inhibitory activity of the TLAM isomers.
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