منابع مشابه
Small-molecule allosteric activators of sirtuins.
The mammalian sirtuins (SIRT1-7) are NAD(+)-dependent lysine deacylases that play central roles in cell survival, inflammation, energy metabolism, and aging. Members of this family of enzymes are considered promising pharmaceutical targets for the treatment of age-related diseases including cancer, type 2 diabetes, inflammatory disorders, and Alzheimer's disease. SIRT1-activating compounds (STA...
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Fragment-based approaches are used routinely to discover enzyme inhibitors as cellular tools and potential therapeutic agents. There have been few reports, however, of the discovery of small-molecule enzyme activators. Herein, we describe the discovery and characterization of small-molecule activators of a glycoside hydrolase (a bacterial O-GlcNAc hydrolase). A ligand-observed NMR screen of a l...
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The monomeric enzyme GK (glucokinase) has a low affinity for glucose and, quantitatively, is largely expressed in the liver and pancreatic beta-cells, playing a key 'glucose sensing' role to regulate hepatic glucose balance and insulin secretion. Mutations of GK in man can be inactivating, to cause a form of diabetes mellitus, or activating, to lower blood glucose levels. Recently, models of GK...
متن کاملStructure-guided optimization of small molecule c-Abl activators
c-Abl kinase is maintained in its normal inactive state in the cell through an assembled, compact conformation. We describe two chemical series that bind to the myristoyl site of the c-Abl kinase domain and stimulate c-Abl activation. We hypothesize that these molecules activate c-Abl either by blocking the C-terminal helix from adopting a bent conformation that is critical for the formation of...
متن کاملTargeting p53 by small molecule p53 activators in multiple myeloma
For the past three decades of research, p53 has been identified as one of the most targetable molecules for developing anticancer treatments. This tumor suppressor protein is involved in apoptosis, cell cycle arrest and senescence. Impairment of p53 function in tumors occurs either as a result of mutations in the TP53 gene itself or the abrogation of signaling pathways regulating p53 that are r...
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ژورنال
عنوان ژورنال: Biochemical Society Transactions
سال: 2019
ISSN: 0300-5127,1470-8752
DOI: 10.1042/bst20190254