4JPG

2-((1H-benzo[d]imidazol-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-4-ones as Novel PKM2 Activators

4JPG の概要

• エントリーDOI: 10.2210/pdb4jpg/pdb
• 分子名称: Pyruvate kinase isozymes M1/M2, 1,6-di-O-phosphono-beta-D-fructofuranose, 2-(1H-benzimidazol-1-ylmethyl)-4H-pyrido[1,2-a]pyrimidin-4-one, ... (4 entities in total)
• 機能のキーワード: pyruvate kinase, transferase-transferase activator complex, transferase/transferase activator
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 245725.36

構造登録者

Greasley, S.E.,Hickey, M.,Phonephaly, H.,Cronin, C. (登録日: 2013-03-19, 公開日: 2013-05-22, 最終更新日: 2024-02-28)

主引用文献

Guo, C.,Linton, A.,Jalaie, M.,Kephart, S.,Ornelas, M.,Pairish, M.,Greasley, S.,Richardson, P.,Maegley, K.,Hickey, M.,Li, J.,Wu, X.,Ji, X.,Xie, Z.
Discovery of 2-((1H-benzo[d]imidazol-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-4-ones as novel PKM2 activators.
Bioorg.Med.Chem.Lett., 23:3358-3363, 2013

PubMed Abstract: The M2 isoform of pyruvate kinase is an emerging target for antitumor therapy. In this letter, we describe the discovery of 2-((1H-benzo[d]imidazol-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-4-ones as potent and selective PKM2 activators which were found to have a novel binding mode. The original lead identified from high throughput screening was optimized into an efficient series via computer-aided structure-based drug design. Both a representative compound from this series and an activator described in the literature were used as molecular tools to probe the biological effects of PKM2 activation on cancer cells. Our results suggested that PKM2 activation alone is not sufficient to alter cancer cell metabolism.

PubMed: 23622982
DOI: 10.1016/j.bmcl.2013.03.090

実験手法

X-RAY DIFFRACTION (2.33 Å)