5WI0

Crystal structure of human NAMPT with fragment 2: 2-[(2-fluorophenyl)amino]-6-propylpyrimidin-4(3H)-one

5WI0 の概要

• エントリーDOI: 10.2210/pdb5wi0/pdb
• 分子名称: Nicotinamide phosphoribosyltransferase, 2-[(2-fluorophenyl)amino]-6-propylpyrimidin-4(3H)-one (3 entities in total)
• 機能のキーワード: nampt, inhibitor, 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: 2
• 化学式量合計: 111684.41

構造登録者

Longenecker, K.L.,Raich, D.,Korepanova, A.V. (登録日: 2017-07-18, 公開日: 2018-01-10, 最終更新日: 2023-10-04)

主引用文献

Korepanova, A.,Longenecker, K.L.,Pratt, S.D.,Panchal, S.C.,Clark, R.F.,Lake, M.,Gopalakrishnan, S.M.,Raich, D.,Sun, C.,Petros, A.M.
Fragment-based discovery of a potent NAMPT inhibitor.
Bioorg. Med. Chem. Lett., 28:437-440, 2018

PubMed Abstract: NAMPT expression is elevated in many cancers, making this protein a potential target for anticancer therapy. We have carried out both NMR based and TR-FRET based fragment screens against human NAMPT and identified six novel binders with a range of potencies. Co-crystal structures were obtained for two of the fragments bound to NAMPT while for the other four fragments force-field driven docking was employed to generate a bound pose. Based on structural insights arising from comparison of the bound fragment poses to that of bound FK866 we were able to synthetically elaborate one of the fragments into a potent NAMPT inhibitor.

PubMed: 29287958
DOI: 10.1016/j.bmcl.2017.12.023

実験手法

X-RAY DIFFRACTION (2.05 Å)