4G9C

Human B-Raf Kinase Domain bound to a Type II Pyrazolopyridine Inhibitor

4G9C の概要

• エントリーDOI: 10.2210/pdb4g9c/pdb
• 関連するPDBエントリー: 4G9R
• 分子名称: Serine/threonine-protein kinase B-raf, 3-{[3-(2-cyanopropan-2-yl)benzoyl]amino}-2,6-difluoro-N-(3-methoxy-2H-pyrazolo[3,4-b]pyridin-5-yl)benzamide (2 entities in total)
• 機能のキーワード: dfg-out, inhibitor, type ii, transferase, kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus (By similarity): P15056
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 71416.19

構造登録者

Voegtli, W.C.,Sturgis, H.L. (登録日: 2012-07-23, 公開日: 2012-11-14, 最終更新日: 2024-02-28)

主引用文献

Wenglowsky, S.,Moreno, D.,Laird, E.R.,Gloor, S.L.,Ren, L.,Risom, T.,Rudolph, J.,Sturgis, H.L.,Voegtli, W.C.
Pyrazolopyridine inhibitors of B-Raf(V600E). Part 4: Rational design and kinase selectivity profile of cell potent type II inhibitors.
Bioorg.Med.Chem.Lett., 22:6237-6241, 2012

PubMed Abstract: Cell potent inhibitors of B-Raf(V600E) that bind to the kinase in the DFG-out conformation are reported. These compounds utilize the hinge-binding group and lipophilic linker from a previously disclosed series of B-Raf(V600E) inhibitors that bind to the kinase in an atypical DFG-in, αC-helix-out conformation. This new series demonstrates that DFG-out kinase inhibitors can be rationally designed from related inhibitors which utilize an unconventional binding mode. Kinase selectivity profiles are compared. The pattern of kinase selectivity was found to be determined by the feature of the inhibitor which extends into the back pocket of the kinase and leads to the kinase conformation, rather than by the hinge-binding group or other minor modifications.

PubMed: 22954737
DOI: 10.1016/j.bmcl.2012.08.007

実験手法

X-RAY DIFFRACTION (3.5 Å)