Characterization of Binding Mode for Human Coagulation Factor XI (FXI) Inhibitors

Bulletin of the Korean chemical society

Jun Tae Kim¹  Jae Eun Cho¹  Nam Sook Kang¹  Seo Hee Jung¹ 

关键词: Human coagulation factor XIa (FXIa);    Three dimensional quantitative structure activity relationship (3D QSAR);    Comparative molecular field analysis (CoMFA);    Comparative molecular similarity indices analysis (CoMSIA);    Docking;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

The human coagulation factor XI (FXI) is a serine protease that plays a significant role in blocking of the blood coagulation cascade as an attractive antithrombotic target. Selective inhibition of FXIa (an activated form of factor XI) disrupts the intrinsic coagulation pathway without affecting the extrinsic pathway or other coagulation factors such as FXa, FIIa, FVIIa. Furthermore, targeting the FXIa might significantly reduce the bleeding side effects and improve the safety index. This paper reports on a docking-based three dimensional quantitative structure activity relationship (3D-QSAR) study of the potent FXIa inhibitors, the chloro-phenyl tetrazole scaffold series, using comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) methods. Due to the characterization of FXIa binding site, we classified the alignment of the known FXIa inhibitors into two groups according to the docked pose: S1-S2-S4 and S1-S1`- S2`. Consequently, highly predictive 3D-QSAR models of our result will provide insight for designing new potent FXIa inhibitors.

【 授权许可】

Unknown