1356354-09-0Relevant articles and documents
T-3364366 Targets the Desaturase Domain of Delta-5 Desaturase with Nanomolar Potency and a Multihour Residence Time
Miyahisa, Ikuo,Suzuki, Hideo,Mizukami, Atsushi,Tanaka, Yukiya,Ono, Midori,Hixon, Mark S.,Matsui, Junji
supporting information, p. 868 - 872 (2016/10/12)
Delta-5 desaturase (D5D) catalyzes the conversion from dihomo-gamma linoleic acid (DGLA) to arachidonic acid (AA). DGLA and AA are common precursors of anti- and pro-inflammatory eicosanoids, respectively, making D5D an attractive drug target for inflammatory-related diseases. Despite several reports on D5D inhibitors, their biochemical mechanisms of action (MOAs) remain poorly understood, primarily due to the difficulty in performing quantitative enzymatic analysis. Herein, we report a radioligand binding assay to overcome this challenge and characterized T-3364366, a thienopyrimidinone D5D inhibitor, by use of the assay. T-3364366 is a reversible, slow-binding inhibitor with a dissociation half-life in excess of 2.0 h. The long residence time was confirmed in cellular washout assays. Domain swapping experiments between D5D and D6D support [3H]T-3364366 binding to the desaturase domain of D5D. The present study is the first to demonstrate biochemical MOA of desaturase inhibitors, providing important insight into drug discovery of desaturase enzymes.
FUSED HETEROCYCLIC COMPOUND AND APPLICATION THEREOF
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Paragraph 0674; 0675; 0676, (2013/06/04)
The present invention provides a compound useful for the prophylaxis or treatment of eicosanoid-associated diseases such as atherosclerosis, atherothrombosis, diabetes, obesity, asthma, fever, pain, cancer, rheumatism, osteoarthritis, atopic dermatitis and the like, and having superior pharmacological action, physicochemical properties and the like. The present invention relates to a compound represented by the following formula: wherein each symbol is as defined in the specification, or a salt thereof.