Dual-targeted Drug Design of HER2 and HSP90 by CoMFA Model and Pharmacophore Analysis

被引：0

作者：

Huang, Hung-Jin ^{[1
]}

Bau, Da-Tian ^{[1
,2
,3
]}

Tsai, Ming-Hsui ^{[3
]}

Hsu, Yuan-Man ^{[1
]}

Ho, Tin-Yun ^{[2
]}

Chen, Chien-Yu ^{[1
]}

Chang, Yea-Huey ^{[1
]}

Tsai, Fuu-Jen ^{[4
,5
,6
]}

Tsai, Chang-Hai ^{[7
]}

Chen, Calvin Yu-Chian ^{[1
,2
,3
,4
]}

机构：

[1] China Med Univ, Dept Biol Sci & Technol, Lab Pharmacoinformat & Nanotechnol, Taichung 40402, Taiwan

[2] China Med Univ, Grad Inst Chinese Med Sci, Taichung 40402, Taiwan

[3] China Med Univ, Terry Fox Canc Res Lab, Taichung 40402, Taiwan

[4] Univ Asia, Dept Bioinformat, Taichung 41354, Taiwan

[5] China Med Univ Hosp, Dept Med Genet Pediatr & Med Res, Taichung 404029, Taiwan

[6] China Med Univ, Coll Chinese Med, Taichung 40402, Taiwan

[7] Univ Asia, Dept Healthcare Adm, Taichung 41354, Taiwan

来源：

PROCEEDINGS OF THE 2009 2ND INTERNATIONAL CONFERENCE ON BIOMEDICAL ENGINEERING AND INFORMATICS, VOLS 1-4 | 2009年

关键词：

HER2; HSP90; Dual target; CoMFA; TYROSINE KINASE; INHIBITORS; DERIVATIVES; BINDING; CANCER; ZD6474;

D O I：

暂无

中图分类号：

TP18 [人工智能理论];

学科分类号：

081104 ; 0812 ; 0835 ; 1405 ;

摘要：

Heat shock protein 90 (HSP90) and human epidermal growth factor receptor 2 protein (HER2) are involved in several signal pathways for cancer cell proliferation. We focused on these two hallmarkers to design the dual-targeted inhibitors for cancer therapy. The comparative molecular field analysis (CoMFA) and pharmacophore analysis were employed for generating the predictive models. According the leave-one out (LOO) cross-validation, the CoMFA models obtained the significant r2 values of 0.978 and 0.974 for HSP90 and HER2, respectively. The contour maps of both targets indicated that there were amount of similar bulky favors area. Besides, the cost difference of pharmacophore models was 48.539 for 70% correlation with the experiment. The queries at 3-N and 6-N position of purine-based compound had the similar distributions. This study provided important information for design the HER2 and HSP90 dual-targeted inhibitors

引用

页码：837 / +

页数：3

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