Discovery of Novel DUSP4 Inhibitors through the Virtual Screening with Docking Simulations

Bulletin of the Korean chemical society

Sung Min Oh¹  Hwangseo Park¹  So Ya Park¹  Seong Eon Ryu¹  Tae Jin Jeon¹  Seung Jun Kim¹  Pham Ngoc Chien¹ 

关键词: Virtual screening;    Docking;    DUSP4;    Inhibitor;    Drug design;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

Dual specificity protein phosphatase 4 (DUSP4) has been considered a promising target for the development of therapeutics for various human cancers. Here, we report the first example for a successful application of the structure-based virtual screening to identify the novel small-molecule DUSP4 inhibitors. As a consequence of the virtual screening with the modified scoring function to include an effective molecular solvation free energy term, five micromolar DUSP4 inhibitors are found with the associated IC50 values ranging from 3.5 to 10.8 μM. Because these newly identified inhibitors were also screened for having desirable physicochemical properties as a drug candidate, they may serve as a starting point of the structure-activity relationship study to optimize the medical efficacy. Structural features relevant to the stabilization of the new inhibitors in the active site of DUSP4 are discussed in detail.

【 授权许可】

Unknown