Product Details of 91912-53-7. Aromatic compounds can be divided into two categories: single heterocycles and fused heterocycles. Compound: 3-(Pyridin-4-yl)-1H-pyrazol-5-amine, is researched, Molecular C8H8N4, CAS is 91912-53-7, about Structure-activity relationship study, target identification, and pharmacological characterization of a small molecular IL-12/23 inhibitor, APY0201. Author is Hayakawa, Nobuhiko; Noguchi, Masatsugu; Takeshita, Sen; Eviryanti, Agung; Seki, Yukie; Nishio, Hikaru; Yokoyama, Ryohei; Noguchi, Misato; Shuto, Manami; Shima, Yoichiro; Kuribayashi, Kanna; Kageyama, Shunsuke; Eda, Hiroyuki; Suzuki, Manabu; Hatta, Tomohisa; Iemura, Shun-ichiro; Natsume, Tohru; Tanabe, Itsuya; Nakagawa, Ryusuke; Shiozaki, Makoto; Sakurai, Kuniya; Shoji, Masataka; Andou, Ayatoshi; Yamamoto, Takashi.
Interleukin-12 (IL-12) and IL-23 are proinflammatory cytokines and therapeutic targets for inflammatory and autoimmune diseases, including inflammatory bowel diseases, psoriasis, rheumatoid arthritis, and multiple sclerosis. The authors describe the discovery of APY0201, a unique small mol. IL-12/23 production inhibitor, from activated macrophages and monocytes, and demonstrate ameliorated inflammation in an exptl. model of colitis. Through a chem. proteomics approach using a highly sensitive direct nanoflow LC-MS/MS system and bait compounds equipped with the FLAG epitope associated regulator of PIKfyve (ArPIKfyve) was detected. Further study identified its associated protein phosphoinositide kinase, FYVE finger-containing (PIKfyve), as the target protein of APY0201, which was characterized as a potent, highly selective, ATP-competitive PIKfyve inhibitor that interrupts the conversion of phosphatidylinositol 3-phosphate (PtdIns3P) to PtdIns(3,5)P2. These results elucidate the function of PIKfyve kinase in the IL-12/23 production pathway and in IL-12/23-driven inflammatory disease pathologies to provide a compelling rationale for targeting PIKfyve kinase in inflammatory and autoimmune diseases.
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