Publications by authors named "Donatella Rescigno"
Article Synopsis
- - Researchers developed new ALK5 inhibitors aimed at treating diseases like cancer and fibrosis, focusing on a specific chemical structure called a 4,6-disubstituted pyridazine core.
- - They used a method called "scaffold-hopping" to explore different chemical frameworks and found a particularly effective compound that was enhanced for inhalation, reducing the risk of side effects.
- - The optimized ALK5 inhibitors demonstrated improved effectiveness and properties for lung retention, suggesting they could be good candidates for creating new inhaled treatment options.
Article Synopsis
- Protein arginine methyltransferases (PRMTs) are key targets for therapy due to their role in many cellular processes and their connection to various diseases.
- The study introduces a deconstruction-reconstruction approach that led to the discovery of potent and selective inhibitors specifically targeting PRMT4, which reduced arginine methylation levels and cell proliferation in MCF7 cells.
- Crystal structures of different PRMTs are provided, reinforcing the findings of specificity and selectivity of the newly identified inhibitors.
Since the discovery of compound BIX01294 over 10 years ago, only a very limited number of nonquinazoline inhibitors of H3K9-specific methyltransferases G9a and G9a-like protein (GLP) have been reported. Herein, we report the identification of a novel chemotype for G9a/GLP inhibitors, based on the underinvestigated 2-alkyl-5-amino- and 2-aryl-5-amino-substituted 3 H-benzo[ e][1,4]diazepine scaffold. Our research efforts resulted in the identification 12a (EML741), which not only maintained the high in vitro and cellular potency of its quinazoline counterpart, but also displayed improved inhibitory potency against DNA methyltransferase 1, improved selectivity against other methyltransferases, low cell toxicity, and improved apparent permeability values in both parallel artificial membrane permeability assay (PAMPA) and blood-brain barrier-specific PAMPA, and therefore might potentially be a better candidate for animal studies.
View Article and Find Full Text PDFSETD8/SET8/Pr-SET7/KMT5A is the only known lysine methyltransferase (KMT) that monomethylates lysine 20 of histone H4 (H4K20) in vivo. Lysine residues of non-histone proteins including proliferating cell nuclear antigen (PCNA) and p53 are also monomethylated. As a consequence, the methyltransferase activity of the enzyme is implicated in many essential cellular processes including DNA replication, DNA damage response, transcription modulation, and cell cycle regulation.
View Article and Find Full Text PDFSETD8/SET8/Pr-SET7/KMT5A is the only known lysine methyltransferase that monomethylates lysine 20 of histone H4 (H4K20) in vivo. The methyltransferase activity of SETD8 has been implicated in many essential cellular processes, including DNA replication, DNA damage response, transcription modulation, and cell cycle regulation. In addition to H4K20, SETD8 monomethylates non-histone substrates including proliferating cell nuclear antigen and p53.
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