2OFU

x-ray crystal structure of 2-aminopyrimidine carbamate 43 bound to Lck

2OFU の概要

• エントリーDOI: 10.2210/pdb2ofu/pdb
• 分子名称: Proto-oncogene tyrosine-protein kinase LCK, SULFATE ION, 2,6-DIMETHYLPHENYL 2-(3,5-DIMETHOXY-4-(3-(4-METHYLPIPERAZIN-1-YL)PROPOXY)PHENYLAMINO)PYRIMIDIN- 4-YL(2,4-DIMETHOXYPHENYL)CARBAMATE, ... (4 entities in total)
• 機能のキーワード: lck, kinase domain, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P06239
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32433.97

構造登録者

Huang, X. (登録日: 2007-01-04, 公開日: 2007-02-27, 最終更新日: 2024-11-20)

主引用文献

Martin, M.W.,Newcomb, J.,Nunes, J.J.,McGowan, D.C.,Armistead, D.M.,Boucher, C.,Buchanan, J.L.,Buckner, W.,Chai, L.,Elbaum, D.,Epstein, L.F.,Faust, T.,Flynn, S.,Gallant, P.,Gore, A.,Gu, Y.,Hsieh, F.,Huang, X.,Lee, J.H.,Metz, D.,Middleton, S.,Mohn, D.,Morgenstern, K.,Morrison, M.J.,Novak, P.M.,Oliveira-dos-Santos, A.,Powers, D.,Rose, P.,Schneider, S.,Sell, S.,Tudor, Y.,Turci, S.M.,Welcher, A.A.,White, R.D.,Zack, D.,Zhao, H.,Zhu, L.,Zhu, X.,Ghiron, C.,Amouzegh, P.,Ermann, M.,Jenkins, J.,Johnston, D.,Napier, S.,Power, E.
Novel 2-Aminopyrimidine Carbamates as Potent and Orally Active Inhibitors of Lck: Synthesis, SAR, and in Vivo Antiinflammatory Activity
J.Med.Chem., 49:4981-, 2006

PubMed Abstract: The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and NK cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. A small molecule inhibitor of Lck is expected to be useful in the treatment of T cell-mediated autoimmune and inflammatory disorders and/or organ transplant rejection. In this paper, we describe the synthesis, structure-activity relationships, and pharmacological characterization of 2-aminopyrimidine carbamates, a new class of compounds with potent and selective inhibition of Lck. The most promising compound of this series, 2,6-dimethylphenyl 2-((3,5-bis(methyloxy)-4-((3-(4-methyl-1-piperazinyl)propyl)oxy)phenyl)amino)-4-pyrimidinyl(2,4-bis(methyloxy)phenyl)carbamate (43) exhibits good activity when evaluated in in vitro assays and in an in vivo model of T cell activation.

PubMed: 16884310
DOI: 10.1021/jm060435i

実験手法

X-RAY DIFFRACTION (2 Å)