3E64

Fragment based discovery of JAK-2 inhibitors

3E64 の概要

• エントリーDOI: 10.2210/pdb3e64/pdb
• 関連するPDBエントリー: 3E62 3E63
• 分子名称: Tyrosine-protein kinase JAK2, 4-(3-amino-1H-indazol-5-yl)-N-tert-butylbenzenesulfonamide (3 entities in total)
• 機能のキーワード: drug discovery, jak2, fragment based, atp-binding, disease mutation, kinase, membrane, nucleotide-binding, phosphoprotein, proto-oncogene, sh2 domain, transferase, tyrosine-protein kinase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endomembrane system; Peripheral membrane protein (By similarity): O60674
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35022.93

構造登録者

Antonysamy, S.,Fang, W.,Hirst, G.,Park, F.,Russell, M.,Smyth, L.,Sprengeler, P.,Stappenbeck, F.,Steensma, R.,Thompson, D.A.,Wilson, M.,Wong, M.,Zhang, A.,Zhang, F. (登録日: 2008-08-14, 公開日: 2008-10-14, 最終更新日: 2024-10-16)

主引用文献

Antonysamy, S.,Hirst, G.,Park, F.,Sprengeler, P.,Stappenbeck, F.,Steensma, R.,Wilson, M.,Wong, M.
Fragment-based discovery of JAK-2 inhibitors.
Bioorg.Med.Chem.Lett., 19:279-282, 2009

PubMed Abstract: Fragment-based hit identification coupled with crystallographically enabled structure-based drug design was used to design potent inhibitors of JAK-2. After two iterations from fragment 1, we were able to increase potency by greater than 500-fold to provide sulfonamide 13, a 78-nM JAK-2 inhibitor.

PubMed: 19019674
DOI: 10.1016/j.bmcl.2008.08.064

実験手法

X-RAY DIFFRACTION (1.8 Å)