5CF5

CRYSTAL STRUCTURE OF JANUS KINASE 2 IN COMPLEX WITH N,N-DICYCLOPROPYL-7-[(DIMETHYL-1,3-THIAZOL-2-YL)AMINO]-10-ETHYL-3-METHYL-3,5,8,10-TETRAAZATRICYCLO[7.3.0.02,6] DODECA-1(9),2(6),4,7,11-PENTAENE-11-CARBOXAMIDE

5CF5 の概要

• エントリーDOI: 10.2210/pdb5cf5/pdb
• 関連するPDBエントリー: 5CF4 5CF6 5CF8
• 分子名称: Tyrosine-protein kinase JAK2, N,N-dicyclopropyl-4-[(4,5-dimethyl-1,3-thiazol-2-yl)amino]-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (3 entities in total)
• 機能のキーワード: kinase, transferase, transferase-transferase inhibitor complex, transferase/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: 2
• 化学式量合計: 76633.09

構造登録者

Sack, J.S. (登録日: 2015-07-08, 公開日: 2015-08-26, 最終更新日: 2024-11-20)

主引用文献

Hart, A.C.,Schroeder, G.M.,Wan, H.,Grebinski, J.,Inghrim, J.,Kempson, J.,Guo, J.,Pitts, W.J.,Tokarski, J.S.,Sack, J.S.,Khan, J.A.,Lippy, J.,Lorenzi, M.V.,You, D.,McDevitt, T.,Vuppugalla, R.,Zhang, Y.,Lombardo, L.J.,Trainor, G.L.,Purandare, A.V.
Structure-Based Design of Selective Janus Kinase 2 Imidazo[4,5-d]pyrrolo[2,3-b]pyridine Inhibitors.
Acs Med.Chem.Lett., 6:845-849, 2015

PubMed Abstract: Early hit to lead work on a pyrrolopyridine chemotype provided access to compounds with biochemical and cellular potency against Janus kinase 2 (JAK2). Structure-based drug design along the extended hinge region of JAK2 led to the identification of an important H-bond interaction with the side chain of Tyr 931, which improved JAK family selectivity. The 4,5-dimethyl thiazole analogue 18 demonstrated high levels of JAK family selectivity and was identified as a promising lead for the program.

PubMed: 26288682
DOI: 10.1021/acsmedchemlett.5b00225

実験手法

X-RAY DIFFRACTION (2.45 Å)