4YZU

Rapid development of two Factor IXa inhibitors from Hit to Lead

4YZU の概要

• エントリーDOI: 10.2210/pdb4yzu/pdb
• 関連するPDBエントリー: 4Z0K
• 分子名称: Coagulation factor IX, N-[2-(5,6-dimethyl-1H-benzimidazol-2-yl)ethyl]-4-(4H-1,2,4-triazol-4-yl)benzamide, SODIUM ION, ... (7 entities in total)
• 機能のキーワード: serine proteinase, blood coagulation, coagulation factor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Secreted : P00740 P00740
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33572.66

構造登録者

Hruza, A.,Reichert, P. (登録日: 2015-03-25, 公開日: 2015-05-20, 最終更新日: 2024-10-23)

主引用文献

Parker, D.L.,Walsh, S.,Li, B.,Kim, E.,Sharipour, A.,Smith, C.,Chen, Y.H.,Berger, R.,Harper, B.,Zhang, T.,Park, M.,Shu, M.,Wu, J.,Xu, J.,Dewnani, S.,Sherer, E.C.,Hruza, A.,Reichert, P.,Geissler, W.,Sonatore, L.,Ellsworth, K.,Balkovec, J.,Greenlee, W.,Wood, H.B.
Rapid development of two factor IXa inhibitors from hit to lead.
Bioorg.Med.Chem.Lett., 25:2321-2325, 2015

PubMed Abstract: Two high-throughput screening hits were investigated for SAR against human factor IXa. Both hits feature a benzamide linked to a [6-5]-heteroaryl via an alkyl amine. In the case where this system is a benzimidazolyl-ethyl amine the binding potency for the hit was improved >500-fold, from 9 μM to 0.016 μM. For the other hit, which contains a tetrahydropyrido-indazole amine, potency was improved 20-fold, from 2 μM to 0.09 μM. X-ray crystal structures were obtained for an example of each class which improved understanding of the binding, and will enable further drug discovery efforts.

PubMed: 25937013
DOI: 10.1016/j.bmcl.2015.04.025

実験手法

X-RAY DIFFRACTION (1.41 Å)