4R93

BACE-1 in complex with (R)-4-(2-cyclohexylethyl)-1-methyl-5-oxo-4-(((1S,3R)-3-(3-phenylureido)cyclohexyl)methyl)imidazolidin-2-iminium

4R93 の概要

• エントリーDOI: 10.2210/pdb4r93/pdb
• 関連するPDBエントリー: 4R8Y 4R91 4R92 4R95
• 分子名称: Beta-secretase 1, L(+)-TARTARIC ACID, 1-[(1R,3S)-3-{[(2E,4R)-4-(2-cyclohexylethyl)-2-imino-1-methyl-5-oxoimidazolidin-4-yl]methyl}cyclohexyl]-3-phenylurea, ... (4 entities in total)
• 機能のキーワード: aspartic protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P56817
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 93857.35

構造登録者

Orth, P.,Strickland, C.,Caldwell, J.P. (登録日: 2014-09-03, 公開日: 2014-11-05, 最終更新日: 2024-11-06)

主引用文献

Caldwell, J.P.,Mazzola, R.D.,Durkin, J.,Chen, J.,Chen, X.,Favreau, L.,Kennedy, M.,Kuvelkar, R.,Lee, J.,McHugh, N.,McKittrick, B.,Orth, P.,Stamford, A.,Strickland, C.,Voigt, J.,Wang, L.,Zhang, L.,Zhang, Q.,Zhu, Z.
Discovery of potent iminoheterocycle BACE1 inhibitors.
Bioorg.Med.Chem.Lett., 24:5455-5459, 2014

PubMed Abstract: The synthesis of a series of iminoheterocycles and their structure-activity relationships (SAR) as inhibitors of the aspartyl protease BACE1 will be detailed. An effort to access the S3 subsite directly from the S1 subsite initially yielded compounds with sub-micromolar potency. A subset of compounds from this effort unexpectedly occupied a different binding site and displayed excellent BACE1 affinities. Select compounds from this subset acutely lowered Aβ40 levels upon subcutaneous and oral administration to rats.

PubMed: 25455483
DOI: 10.1016/j.bmcl.2014.10.006

実験手法

X-RAY DIFFRACTION (1.71 Å)