4YD0

Influenza polymerase basic protein 2 (PB2) bound to an azaindole-tetrazole inhibitor

4YD0 の概要

• エントリーDOI: 10.2210/pdb4yd0/pdb
• 分子名称: Polymerase basic protein 2, 2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-N-[(1R,2S,3S,4R)-3-(1H-tetrazol-5-yl)bicyclo[2.2.2]oct-2-yl]pyrimidin-4-amine (3 entities in total)
• 機能のキーワード: small-molecule drug, inhibitor, flu, m7-gtp pocket, transcription-inhibitor complex, transcription/inhibitor
• 由来する生物種: Influenza A virus
• 細胞内の位置: Virion: Q30NP1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19614.20

構造登録者

Jacobs, M.D. (登録日: 2015-02-20, 公開日: 2015-04-15, 最終更新日: 2024-02-28)

主引用文献

Boyd, M.J.,Bandarage, U.K.,Bennett, H.,Byrn, R.R.,Davies, I.,Gu, W.,Jacobs, M.,Ledeboer, M.W.,Ledford, B.,Leeman, J.R.,Perola, E.,Wang, T.,Bennani, Y.,Clark, M.P.,Charifson, P.S.
Isosteric replacements of the carboxylic acid of drug candidate VX-787: Effect of charge on antiviral potency and kinase activity of azaindole-based influenza PB2 inhibitors.
Bioorg.Med.Chem.Lett., 25:1990-1994, 2015

PubMed Abstract: VX-787 is a first in class, orally bioavailable compound that offers unparalleled potential for the treatment of pandemic and seasonal influenza. As a part of our routine SAR exploration, carboxylic acid isosteres of VX-787 were prepared and tested against influenza A. It was found that the negative charge is important for maintaining potency and selectivity relative to kinase targets. Neutral carboxylic acid replacements generally resulted in compounds that were significantly less potent and less selective relative to the charged species.

PubMed: 25827523
DOI: 10.1016/j.bmcl.2015.03.013

実験手法

X-RAY DIFFRACTION (2.62 Å)