4C61

Inhibitors of Jak2 Kinase domain

4C61 の概要

• エントリーDOI: 10.2210/pdb4c61/pdb
• 関連するPDBエントリー: 4C62
• 分子名称: TYROSINE-PROTEIN KINASE JAK2, N2-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-7-methyl-N4-(1-methylimidazol-4-yl)thieno[3,2-d]pyrimidine-2,4-diamine, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: kinase, transferase
• 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: 2
• 化学式量合計: 71137.63

構造登録者

Read, J.A.,Green, I.,Pollard, H.,Howard, T. (登録日: 2013-09-17, 公開日: 2014-01-08, 最終更新日: 2024-11-06)

主引用文献

Su, Q.,Ioannidis, S.,Chuaqui, C.,Almeida, L.,Alimzhanov, M.,Bebernitz, G.,Bell, K.,Block, M.,Howard, T.,Huang, S.,Huszar, D.,Read, J.A.,Rivard Costa, C.,Shi, J.,Su, M.,Ye, M.,Zinda, M.
Discovery of 1-Methyl-1H-Imidazole Derivatives as Potent Jak2 Inhibitors.
J.Med.Chem., 57:144-, 2014

PubMed Abstract: Structure based design, synthesis, and biological evaluation of a novel series of 1-methyl-1H-imidazole, as potent Jak2 inhibitors to modulate the Jak/STAT pathway, are described. Using the C-ring fragment from our first clinical candidate AZD1480 (24), optimization of the series led to the discovery of compound 19a, a potent, orally bioavailable Jak2 inhibitor. Compound 19a displayed a high level of cellular activity in hematopoietic cell lines harboring the V617F mutation and in murine BaF3 TEL-Jak2 cells. Compound 19a demonstrated significant tumor growth inhibition in a UKE-1 xenograft model within a well-tolerated dose range.

PubMed: 24359159
DOI: 10.1021/JM401546N

実験手法

X-RAY DIFFRACTION (2.45 Å)