4BBF

Aminoalkylpyrimidine Inhibitor Complexes with JAK2

4BBF の概要

• エントリーDOI: 10.2210/pdb4bbf/pdb
• 関連するPDBエントリー: 2B7A 2W1I 2XA4 4AQC 4BBE
• 分子名称: TYROSINE-PROTEIN KINASE JAK2, (2R)-N-[4-[2-[(4-morpholin-4-ylphenyl)amino]pyrimidin-4-yl]phenyl]pyrrolidine-2-carboxamide (3 entities in total)
• 機能のキーワード: transferase, inhibitor
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Endomembrane system ; Peripheral membrane protein : O60674
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 141758.20

構造登録者

Li, J. (登録日: 2012-09-21, 公開日: 2012-11-21, 最終更新日: 2024-05-01)

主引用文献

Forsyth, T.,Kearney, P.C.,Kim, B.G.,Johnson, H.W.B.,Aay, N.,Arcalas, A.,Brown, D.S.,Chan, V.,Chen, J.,Du, H.,Epshteyn, S.,Galan, A.A.,Huynh, T.P.,Ibrahim, M.A.,Kane, B.,Koltun, E.,Mann, G.,Meyr, L.E.,Lee, M.S.,Lewis, G.L.,Noguchi, R.T.,Pack, M.,Ridgway, B.H.,Shi, X.,Takeuchi, C.S.,Zu, P.,Leahy, J.W.,Nuss, J.M.,Aoyama, R.,Engst, S.,Gendreau, S.B.,Kassees, R.,Li, J.,Lin, S.-H.,Martini, J.-F.,Stout, T.,Tong, P.,Woolfrey, J.,Zhang, W.,Yu, P.
Sar and in Vivo Evaluation of 4-Aryl-2-Aminoalkylpyrimidines as Potent and Selective Janus Kinase 2 (Jak2) Inhibitors
Bioorg.Med.Chem.Lett., 22:7653-, 2012

PubMed Abstract: We report the discovery of a series of 4-aryl-2-aminoalkylpyrimidine derivatives as potent and selective JAK2 inhibitors. High throughput screening of our in-house compound library led to the identification of hit 1, from which optimization resulted in the discovery of highly potent and selective JAK2 inhibitors. Advanced lead 10d demonstrated a significant dose-dependent pharmacodynamic and antitumor effect in a mouse xenograft model. Based upon the desirable profile of 10d (XL019) it was advanced into clinical trials.

PubMed: 23127890
DOI: 10.1016/J.BMCL.2012.10.007

実験手法

X-RAY DIFFRACTION (2 Å)