3ZMG

CRYSTAL STRUCTURE OF BACE-1 IN COMPLEX WITH CHEMICAL LIGAND

3ZMG の概要

• エントリーDOI: 10.2210/pdb3zmg/pdb
• 関連するPDBエントリー: 3ZLQ
• 分子名称: BETA-SECRETASE 1, N-[3-[(4R)-2-azanylidene-5,5-bis(fluoranyl)-4-methyl-1,3-oxazinan-4-yl]-4-fluoranyl-phenyl]-5-cyano-pyridine-2-carboxamide, SODIUM ION, ... (5 entities in total)
• 機能のキーワード: hydrolase
• 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: 46067.45

構造登録者

Banner, D.W.,Kuglstatter, A.,Benz, J.,Stihle, M. (登録日: 2013-02-08, 公開日: 2013-05-01, 最終更新日: 2024-05-01)

主引用文献

Hilpert, H.,Guba, W.,Woltering, T.J.,Wostl, W.,Pinard, E.,Mauser, H.,Mayweg, A.V.,Rogers-Evans, M.,Humm, R.,Krummenacher, D.,Muser, T.,Schnider, C.,Jacobsen, H.,Ozmen, L.,Bergadano, A.,Banner, D.W.,Hochstrasser, R.,Kuglstatter, A.,David-Pierson, P.,Fischer, H.,Polara, A.,Narquizian, R.
Beta-Secretase (Bace1) Inhibitors with High in Vivo Efficacy Suitable for Clinical Evaluation in Alzheimer'S Disease.
J.Med.Chem., 56:3980-, 2013

PubMed Abstract: An extensive fluorine scan of 1,3-oxazines revealed the power of fluorine(s) to lower the pKa and thereby dramatically change the pharmacological profile of this class of BACE1 inhibitors. The CF3 substituted oxazine 89, a potent and highly brain penetrant BACE1 inhibitor, was able to reduce significantly CSF Aβ40 and 42 in rats at oral doses as low as 1 mg/kg. The effect was long lasting, showing a significant reduction of Aβ40 and 42 even after 24 h. In contrast to 89, compound 1b lacking the CF3 group was virtually inactive in vivo.

PubMed: 23590342
DOI: 10.1021/JM400225M

実験手法

X-RAY DIFFRACTION (1.74 Å)