5UPF

Crystal structure of human NAMPT with isoindoline urea inhibitor compound 53

5UPF の概要

• エントリーDOI: 10.2210/pdb5upf/pdb
• 関連するPDBエントリー: 5UPE
• 分子名称: Nicotinamide phosphoribosyltransferase, 5-fluoro-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-2H-isoindole-2-carboxamide (3 entities in total)
• 機能のキーワード: nampt inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus : P43490
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 114030.76

構造登録者

Longenecker, K.L.,Raich, D.,Korepanova, A.V. (登録日: 2017-02-02, 公開日: 2017-06-28, 最終更新日: 2023-10-04)

主引用文献

Curtin, M.L.,Heyman, H.R.,Clark, R.F.,Sorensen, B.K.,Doherty, G.A.,Hansen, T.M.,Frey, R.R.,Sarris, K.A.,Aguirre, A.L.,Shrestha, A.,Tu, N.,Woller, K.,Pliushchev, M.A.,Sweis, R.F.,Cheng, M.,Wilsbacher, J.L.,Kovar, P.J.,Guo, J.,Cheng, D.,Longenecker, K.L.,Raich, D.,Korepanova, A.V.,Soni, N.B.,Algire, M.A.,Richardson, P.L.,Marin, V.L.,Badagnani, I.,Vasudevan, A.,Buchanan, F.G.,Maag, D.,Chiang, G.G.,Tse, C.,Michaelides, M.R.
SAR and characterization of non-substrate isoindoline urea inhibitors of nicotinamide phosphoribosyltransferase (NAMPT).
Bioorg. Med. Chem. Lett., 27:3317-3325, 2017

PubMed Abstract: Herein we disclose SAR studies that led to a series of isoindoline ureas which we recently reported were first-in-class, non-substrate nicotinamide phosphoribosyltransferase (NAMPT) inhibitors. Modification of the isoindoline and/or the terminal functionality of screening hit 5 provided inhibitors such as 52 and 58 with nanomolar antiproliferative activity and preclinical pharmacokinetics properties which enabled potent antitumor activity when dosed orally in mouse xenograft models. X-ray crystal structures of two inhibitors bound in the NAMPT active-site are discussed.

PubMed: 28610984
DOI: 10.1016/j.bmcl.2017.06.018

実験手法

X-RAY DIFFRACTION (1.69 Å)