5KBQ

Pak1 in complex with bis-anilino pyrimidine inhibitor

5KBQ の概要

• エントリーDOI: 10.2210/pdb5kbq/pdb
• 分子名称: Serine/threonine-protein kinase PAK 1, [4-methyl-3-[methyl-[2-[(3-methylsulfonyl-5-morpholin-4-yl-phenyl)amino]pyrimidin-4-yl]amino]phenyl]methanol (3 entities in total)
• 機能のキーワード: serine/threonine-protein kinase pak1, kinase, transferase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : Q13153
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65148.28

構造登録者

Ferguson, A. (登録日: 2016-06-03, 公開日: 2016-09-28, 最終更新日: 2023-09-27)

主引用文献

McCoull, W.,Hennessy, E.J.,Blades, K.,Chuaqui, C.,Dowling, J.E.,Ferguson, A.D.,Goldberg, F.W.,Howe, N.,Jones, C.R.,Kemmitt, P.D.,Lamont, G.,Varnes, J.G.,Ward, R.A.,Yang, B.
Optimization of Highly Kinase Selective Bis-anilino Pyrimidine PAK1 Inhibitors.
ACS Med Chem Lett, 7:1118-1123, 2016

PubMed Abstract: Group I p21-activated kinase (PAK) inhibitors are indicated as important in cancer progression, but achieving high kinase selectivity has been challenging. A bis-anilino pyrimidine PAK1 inhibitor was identified and optimized through structure-based drug design to improve PAK1 potency and achieve high kinase selectivity, giving probe compound (). Reduction of lipophilicity to lower clearance afforded () as an probe compound with oral exposure in mouse. Such probes will allow further investigation of PAK1 biology.

PubMed: 27994749
DOI: 10.1021/acsmedchemlett.6b00322

実験手法

X-RAY DIFFRACTION (2.58 Å)