Li, Xin; Wu, Yizhe; Tian, Gaofei; Jiang, Yixiang; Liu, Zheng; Meng, Xianbin; Bao, Xiucong; Feng, Ling; Sun, Hongyan; Deng, Haiteng; Li, Xiang David published an article in Journal of the American Chemical Society. The title of the article was 《Chemical Proteomic Profiling of Bromodomains Enables the Wide-Spectrum Evaluation of Bromodomain Inhibitors in Living Cells》.Name: 6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-amine The author mentioned the following in the article:
Bromodomains, epigenetic “”readers”” of lysine acetylation marks, exist in different nuclear proteins with diverse biol. functions in chromatin biol. Malfunctions of bromodomains are associated with the pathogenesis of human diseases, such as cancer. Bromodomains have therefore emerged as therapeutic targets for drug discovery. Given the high structural similarity of bromodomains, a critical step in the development of bromodomain inhibitors is the evaluation of their selectivity to avoid off-target effects. While numerous bromodomain inhibitors have been identified, new methods to evaluate the inhibitor selectivity toward endogenous bromodomains in living cells remain needed. Here we report the development of a photoaffinity probe, photo-bromosporine (photo-BS), that enables the wide-spectrum profiling of bromodomain inhibitors in living cells. Photo-BS allowed light-induced crosslinking of recombinant bromodomains and endogenous bromodomain-containing proteins (BCPs) both in vitro and in living cells. The photo-BS-induced labeling of the bromodomains was selectively competed by the corresponding bromodomain inhibitors. Proteomics anal. revealed that photo-BS captured 28 out of the 42 known BCPs from the living cells. Assessment of the two bromodomain inhibitors, bromosporine and GSK6853, resulted in the identification of known as well as previously uncharacterized bromodomain targets. Collectively, we established a chem. proteomics platform to comprehensively evaluate bromodomain inhibitors in terms of their selectivity against endogenous BCPs in living cells. The experimental part of the paper was very detailed, including the reaction process of 6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-amine(cas: 53085-52-2Name: 6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-amine)
6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-amine(cas: 53085-52-2) belongs to anime. The reaction of alkyl halides, R―X, where X is a halogen, or analogous reagents with ammonia (or amines) is useful with certain compounds. Not all alkyl halides are effective reagents; the reaction is sluggish with secondary alkyl groups and fails with tertiary ones. Its usefulness is largely confined to primary alkyl halides (those having two hydrogen atoms on the reacting site).Name: 6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-amine
Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem