Pharmacophore Design for Anti-inflammatory Agent Targeting Interleukin-2 Inducible Tyrosine Kinase (Itk)

Bulletin of the Korean chemical society

Keun Woo Lee¹  Hyong Ha Kim¹  Sugunadevi Sakkiah¹  Sundaraganesan Namadevan¹  Yongseong Kim¹  Meganathan Chandrasekaran¹  Sundarapandian Thangapandian¹ 

关键词: Itk;    Pharmacophore modeling;    Virtual screening;    Docking;    HypoGen;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

A three dimensional pharmacophore model was generated for the molecules which are responsible for anti-inflammatory activities targeting Interleukin-2 inducible tyrosine kinase (Itk). 16 structurally diverse molecules were selected as training set to generate the hypotheses using Discovery Studio v2.1. The best hypothesis, Hypo1, comprises two hydrogen bond acceptor (HBA), one hydrophobic aromatic (HA), one ring aromatic (RA) and shows high cost difference (63.71), high correlation coefficient (0.97) as well as low RMS deviation (0.81). Hypo1 has been further validated toward a test set, decoy set and Fischer’s randomization method. Furthermore, Hypo1 was used to screen NCI and Maybridge databases. Finally, 2 hit molecules were identified as potential leads against Itk, which may be useful for future drug development.

【 授权许可】

Unknown