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4YO6

Irak4-inhibitor co-structure

4YO6 の概要
エントリーDOI10.2210/pdb4yo6/pdb
分子名称Interleukin-1 receptor-associated kinase 4, N-(3-methyl-1-phenyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (3 entities in total)
機能のキーワードkinase, phosphatase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
由来する生物種Homo sapiens (Human)
細胞内の位置Cytoplasm : Q9NWZ3
タンパク質・核酸の鎖数4
化学式量合計137416.45
構造登録者
Fischmann, T.O. (登録日: 2015-03-11, 公開日: 2015-05-20, 最終更新日: 2024-11-06)
主引用文献McElroy, W.T.,Tan, Z.,Ho, G.,Paliwal, S.,Li, G.,Seganish, W.M.,Tulshian, D.,Tata, J.,Fischmann, T.O.,Sondey, C.,Bian, H.,Bober, L.,Jackson, J.,Garlisi, C.G.,Devito, K.,Fossetta, J.,Lundell, D.,Niu, X.
Potent and Selective Amidopyrazole Inhibitors of IRAK4 That Are Efficacious in a Rodent Model of Inflammation.
Acs Med.Chem.Lett., 6:677-682, 2015
Cited by
PubMed Abstract: IRAK4 is a critical upstream kinase in the IL-1R/TLR signaling pathway. Inhibition of IRAK4 is hypothesized to be beneficial in the treatment of autoimmune related disorders. A screening campaign identified a pyrazole class of IRAK4 inhibitors that were determined by X-ray crystallography to exhibit an unusual binding mode. SAR efforts focused on the identification of a potent and selective inhibitor with good aqueous solubility and rodent pharmacokinetics. Pyrazole C-3 piperidines were well tolerated, with N-sulfonyl analogues generally having good rodent oral exposure but poor solubility. N-Alkyl piperidines exhibited excellent solubility and reduced exposure. Pyrazoles possessing N-1 pyridine and fluorophenyl substituents were among the most active. Piperazine 32 was a potent enzyme inhibitor with good cellular activity. Compound 32 reduced the in vivo production of proinflammatory cytokines and was orally efficacious in a mouse antibody induced arthritis disease model of inflammation.
PubMed: 26101573
DOI: 10.1021/acsmedchemlett.5b00106
主引用文献が同じPDBエントリー
実験手法
X-RAY DIFFRACTION (2.32 Å)
構造検証レポート
Validation report summary of 4yo6
検証レポート(詳細版)ダウンロードをダウンロード

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件を2024-11-20に公開中

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