4BI1

Scaffold Focused Virtual Screening: Prospective Application to the Discovery of TTK Inhibitor

4BI1 の概要

• エントリーDOI: 10.2210/pdb4bi1/pdb
• 関連するPDBエントリー: 4BHZ 4BI0 4BI2
• 分子名称: DUAL SPECIFICITY PROTEIN KINASE TTK, 2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL, thieno[3,2-c][2,6]naphthyridine, ... (5 entities in total)
• 機能のキーワード: transferase, protein kinase, mitosis
• 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: 37791.30

構造登録者

Langdon, S.R.,Westwood, I.M.,van Montfort, R.L.M.,Brown, N.,Blagg, J. (登録日: 2013-04-09, 公開日: 2013-05-22, 最終更新日: 2023-12-20)

主引用文献

Langdon, S.R.,Westwood, I.M.,Van Montfort, R.L.M.,Brown, N.,Blagg, J.
Scaffold-Focused Virtual Screening: Prospective Application to the Discovery of Ttk Inhibitors.
J.Chem.Inf.Model, 53:1100-, 2013

PubMed Abstract: We describe and apply a scaffold-focused virtual screen based upon scaffold trees to the mitotic kinase TTK (MPS1). Using level 1 of the scaffold tree, we perform both 2D and 3D similarity searches between a query scaffold and a level 1 scaffold library derived from a 2 million compound library; 98 compounds from 27 unique top-ranked level 1 scaffolds are selected for biochemical screening. We show that this scaffold-focused virtual screen prospectively identifies eight confirmed active compounds that are structurally differentiated from the query compound. In comparison, 100 compounds were selected for biochemical screening using a virtual screen based upon whole molecule similarity resulting in 12 confirmed active compounds that are structurally similar to the query compound. We elucidated the binding mode for four of the eight confirmed scaffold hops to TTK by determining their protein-ligand crystal structures; each represents a ligand-efficient scaffold for inhibitor design.

PubMed: 23672464
DOI: 10.1021/CI400100C

実験手法

X-RAY DIFFRACTION (2.7 Å)