3IOK

2-Aminopyrazolo[1,5-a]pyrimidines as potent and selective inhibitors of JAK2

3IOK の概要

• エントリーDOI: 10.2210/pdb3iok/pdb
• 関連するPDBエントリー: 3IO7
• 分子名称: Tyrosine-protein kinase JAK2, 3-(6-{[(1S)-1-(4-fluorophenyl)ethyl]amino}pyrimidin-4-yl)pyrazolo[1,5-a]pyrimidin-2-amine (3 entities in total)
• 機能のキーワード: kinase, inhibitor, jak2, janus kinase, atp-binding, disease mutation, 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: 37132.17

構造登録者

Zuccola, H.J.,Ledeboer, M.W.,Pierce, A.C. (登録日: 2009-08-14, 公開日: 2009-11-10, 最終更新日: 2024-10-30)

主引用文献

Ledeboer, M.W.,Pierce, A.C.,Duffy, J.P.,Gao, H.,Messersmith, D.,Salituro, F.G.,Nanthakumar, S.,Come, J.,Zuccola, H.J.,Swenson, L.,Shlyakter, D.,Mahajan, S.,Hoock, T.,Fan, B.,Tsai, W.J.,Kolaczkowski, E.,Carrier, S.,Hogan, J.K.,Zessis, R.,Pazhanisamy, S.,Bennani, Y.L.
2-Aminopyrazolo[1,5-a]pyrimidines as potent and selective inhibitors of JAK2.
Bioorg.Med.Chem.Lett., 19:6529-6533, 2009

PubMed Abstract: Constitutive activation of the EPO/JAK2 signaling cascade has recently been implicated in a variety of myeloproliferative disorders including polycythemia vera, essential thrombocythemia and myelofibrosis. In an effort to uncover therapeutic potential of blocking the EPO/JAK2 signaling cascade, we sought to discover selective inhibitors that block the kinase activity of JAK2. Herein, we describe the discovery and structure based optimization of a novel series of 2-amino-pyrazolo[1,5-a]pyrimidines that exhibit potent inhibition of JAK2.

PubMed: 19857967
DOI: 10.1016/j.bmcl.2009.10.053

実験手法

X-RAY DIFFRACTION (2.1 Å)