4F64

Crystal structure of Human Fibroblast Growth Factor Receptor 1 Kinase domain in complex with compound 6

4F64 の概要

• エントリーDOI: 10.2210/pdb4f64/pdb
• 関連するPDBエントリー: 4F63 4F65
• 分子名称: Fibroblast growth factor receptor 1, 5-bromo-N~4~-[3-(3-methoxypropyl)-1H-pyrazol-5-yl]-N~2~-[(3-methyl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: kinase, atp binding, phosphorylation, trans-membrane, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein: P11362
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 71459.57

構造登録者

Norman, R.A.,Breed, J.,Ogg, D. (登録日: 2012-05-14, 公開日: 2012-06-06, 最終更新日: 2023-09-13)

主引用文献

Norman, R.A.,Schott, A.K.,Andrews, D.M.,Breed, J.,Foote, K.M.,Garner, A.P.,Ogg, D.,Orme, J.P.,Pink, J.H.,Roberts, K.,Rudge, D.A.,Thomas, A.P.,Leach, A.G.
Protein-Ligand Crystal Structures Can Guide the Design of Selective Inhibitors of the FGFR Tyrosine Kinase.
J.Med.Chem., 55:5003-5012, 2012

PubMed Abstract: The design of compounds that selectively inhibit a single kinase is a significant challenge, particularly for compounds that bind to the ATP site. We describe here how protein-ligand crystal structure information was able both to rationalize observed selectivity and to guide the design of more selective compounds. Inhibition data from enzyme and cellular screens and the crystal structures of a range of ligands tested during the process of identifying selective inhibitors of FGFR provide a step-by-step illustration of the process. Steric effects were exploited by increasing the size of ligands in specific regions in such a way as to be tolerated in the primary target and not in other related kinases. Kinases are an excellent target class to exploit such approaches because of the conserved fold and small side chain mobility of the active form.

PubMed: 22612866
DOI: 10.1021/jm3004043

実験手法

X-RAY DIFFRACTION (2.05 Å)