Discovery of new potent human protein tyrosine phosphatase inhibitors via pharmacophore and QSAR analysis followed by in silico screening
- 作者：Mutasem O. Taha ; Yasser Bustanji ; Amal G. Al-Bakri ; Al-Motassem Yousef ; Waleed A. Zalloum ; Ihab M. Al-Masri ; Naji Atallah
- 关键词：h-PTP 1B ; Pharmacophore modeling ; QSAR ; In silico screening ; Experimental validation
- 刊名：Journal of Molecular Graphics and Modelling
- 出版年：2007
- 期刊代码：77_10933263
- 类别：cp
- 出版时间：March 2007
- 卷：25
- 期：6
- 页码：870-884
- 文件大小：2239 K
摘要
A pharmacophoric model was developed for human protein tyrosine phosphatase 1B (h-PTP 1B) inhibitors utilizing the HipHop-REFINE module of CATALYST software. Subsequently, genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of physicochemical descriptors and pharmacophore hypothesis that yield consistent QSAR equation of good predictive potential . The validity of the QSAR equation and the associated pharmacophoric hypothesis was experimentally established by the identification of five new h-PTP 1B inhibitors retrieved from the National Cancer Institute (NCI) database.