New inhibitors for the BPTF bromodomain enabled by structural biology and biophysical assay development was written by Ycas, Peter D.;Zahid, Huda;Chan, Alice;Olson, Noelle M.;Johnson, Jorden A.;Talluri, Siva K.;Schonbrunn, Ernst;Pomerantz, William C. K.. And the article was included in Organic & Biomolecular Chemistry in 2020.Product Details of 1619994-69-2 This article mentions the following:
Bromodomain-containing proteins regulate transcription through protein-protein interactions with chromatin and serve as scaffolding proteins for recruiting essential members of the transcriptional machinery. One such protein is the bromodomain and PHD-containing transcription factor (BPTF), the largest member of the nucleosome remodeling complex, NURF. Despite an emerging role for BPTF in regulating a diverse set of cancers, small mol. development for inhibiting the BPTF bromodomain has been lacking. Here we cross-validate three complementary biophys. assays to further the discovery of BPTF bromodomain inhibitors for chem. probe development: two direct binding assays (protein-observed 19F (PrOF) NMR and surface plasmon resonance (SPR)) and a competitive inhibition assay (AlphaScreen). We first compare the assays using three small mols. and acetylated histone peptides with reported affinity for the BPTF bromodomain. Using SPR with both unlabeled and fluorinated BPTF, we further determine that there is a minimal effect of 19F incorporation on ligand binding for future PrOF NMR experiments To guide medicinal chem. efforts towards chem. probe development, we subsequently evaluate two new BPTF inhibitor scaffolds with our suite of biophys. assays and rank-order compound affinities which could not otherwise be determined by PrOF NMR. Finally, we cocrystallize a subset of small mol. inhibitors and present the first published small mol.-protein structures with the BPTF bromodomain. We envision the biophys. assays described here and the structural insights from the crystallog. will guide researchers towards developing selective and potent BPTF bromodomain inhibitors. In the experiment, the researchers used many compounds, for example, Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2Product Details of 1619994-69-2).
Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2) belongs to pyridazine derivatives. Pyridazine-based compounds continued to be a great source of biologically active compounds as evidenced by the number of publications which emerged in 2021. Specifically, the pyridazine moiety is an important structural feature of various pharmacologically important compounds with activities like antimicrobial, analgesic, anti-inflammatory, antiplatelet, anticancer, antisecretory, antiulcer, antidepressant, cardiotonic, vasodilator, antiarrhythmic, and hypocholesterolaemic.Product Details of 1619994-69-2
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Pyridazine | C4H4N2 – PubChem