3OWL

Human CK2 catalytic domain in complex with a benzopyridoindole derivative inhibitor

3OWL の概要

• エントリーDOI: 10.2210/pdb3owl/pdb
• 関連するPDBエントリー: 3MB6 3MB7 3OWJ 3OWK
• 分子名称: CSNK2A1 protein, 11-chloro-8-methyl-7H-benzo[e]pyrido[4,3-b]indol-3-ol, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: serine/threonine-protein kinase, ck2, inhibitor, pyridocarbazol, ellipticine, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40221.14

構造登録者

Reiser, J.-B.,Prudent, R.,Cochet, C. (登録日: 2010-09-20, 公開日: 2010-12-15, 最終更新日: 2024-02-21)

主引用文献

Prudent, R.,Moucadel, V.,Nguyen, C.H.,Barette, C.,Schmidt, F.,Florent, J.C.,Lafanechere, L.,Sautel, C.F.,Duchemin-Pelletier, E.,Spreux, E.,Filhol, O.,Reiser, J.B.,Cochet, C.
Antitumor activity of pyridocarbazole and benzopyridoindole derivatives that inhibit protein kinase CK2.
Cancer Res., 70:9865-9874, 2010

PubMed Abstract: The alkyloid compound ellipticine derived from the berrywood tree is a topoisomerase II poison that is used in ovarian and breast cancer treatment. In this study, we report the identification of ellipticine derivatives and their tetracyclic angular benzopyridoindole analogues as novel ATP-competitive inhibitors of the protein kinase CK2. In vitro and in vivo assays showed that these compounds have a good pharmacologic profile, causing a marked inhibition of CK2 activity associated with cell cycle arrest and apoptosis in human cancer cells. Further, in vivo assays demonstrate antitumor activity in a mouse xenograft model of human glioblastoma. Finally, crystal structures of CK2-inhibitor complex provide structural insights on the molecular basis of CK2 inhibition. Our work lays the foundation for development of clinically useful CK2 inhibitors derived from a well-studied scaffold with suitable pharmacokinetics parameters.

PubMed: 21118972
DOI: 10.1158/0008-5472.CAN-10-0917

実験手法

X-RAY DIFFRACTION (2.1 Å)