Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship Study
The hedgehog signal pathway is an essential agent in developmental patterning, wherein the local concentration of the Hedgehog morphogens directs cellular differentiation and expansion. Furthermore, the Hedgehog pathway has been implicated in tumor/stromal interaction and cancer stem cell. Nowadays...
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| Format: | Article |
| Language: | English |
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MDPI AG
2011-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/12/5/3018/ |
| _version_ | 1811219431131447296 |
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| author | Zhiwei Cao Huiliang Li Ruixin Zhu Qi Liu Jian Tang |
| author_facet | Zhiwei Cao Huiliang Li Ruixin Zhu Qi Liu Jian Tang |
| author_sort | Zhiwei Cao |
| collection | DOAJ |
| description | The hedgehog signal pathway is an essential agent in developmental patterning, wherein the local concentration of the Hedgehog morphogens directs cellular differentiation and expansion. Furthermore, the Hedgehog pathway has been implicated in tumor/stromal interaction and cancer stem cell. Nowadays searching novel inhibitors for Hedgehog Signal Pathway is drawing much more attention by biological, chemical and pharmological scientists. In our study, a solid computational model is proposed which incorporates various statistical analysis methods to perform a Quantitative Structure-Activity Relationship (QSAR) study on the inhibitors of Hedgehog signaling. The whole QSAR data contain 93 cyclopamine derivatives as well as their activities against four different cell lines (NCI-H446, BxPC-3, SW1990 and NCI-H157). Our extensive testing indicated that the binary classification model is a better choice for building the QSAR model of inhibitors of Hedgehog signaling compared with other statistical methods and the corresponding in silico analysis provides three possible ways to improve the activity of inhibitors by demethylation, methylation and hydroxylation at specific positions of the compound scaffold respectively. From these, demethylation is the best choice for inhibitor structure modifications. Our investigation also revealed that NCI-H466 served as the best cell line for testing the activities of inhibitors of Hedgehog signal pathway among others. |
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| format | Article |
| id | doaj.art-25814213988c4a59b8c9b77356ddbf47 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T07:25:38Z |
| publishDate | 2011-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-25814213988c4a59b8c9b77356ddbf472022-12-22T03:42:12ZengMDPI AGInternational Journal of Molecular Sciences1422-00672011-05-011253018303310.3390/ijms12053018Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship StudyZhiwei CaoHuiliang LiRuixin ZhuQi LiuJian TangThe hedgehog signal pathway is an essential agent in developmental patterning, wherein the local concentration of the Hedgehog morphogens directs cellular differentiation and expansion. Furthermore, the Hedgehog pathway has been implicated in tumor/stromal interaction and cancer stem cell. Nowadays searching novel inhibitors for Hedgehog Signal Pathway is drawing much more attention by biological, chemical and pharmological scientists. In our study, a solid computational model is proposed which incorporates various statistical analysis methods to perform a Quantitative Structure-Activity Relationship (QSAR) study on the inhibitors of Hedgehog signaling. The whole QSAR data contain 93 cyclopamine derivatives as well as their activities against four different cell lines (NCI-H446, BxPC-3, SW1990 and NCI-H157). Our extensive testing indicated that the binary classification model is a better choice for building the QSAR model of inhibitors of Hedgehog signaling compared with other statistical methods and the corresponding in silico analysis provides three possible ways to improve the activity of inhibitors by demethylation, methylation and hydroxylation at specific positions of the compound scaffold respectively. From these, demethylation is the best choice for inhibitor structure modifications. Our investigation also revealed that NCI-H466 served as the best cell line for testing the activities of inhibitors of Hedgehog signal pathway among others.http://www.mdpi.com/1422-0067/12/5/3018/QSARHedgehog signal pathwayinhibitorcyclopamine |
| spellingShingle | Zhiwei Cao Huiliang Li Ruixin Zhu Qi Liu Jian Tang Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship Study International Journal of Molecular Sciences QSAR Hedgehog signal pathway inhibitor cyclopamine |
| title | Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship Study |
| title_full | Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship Study |
| title_fullStr | Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship Study |
| title_full_unstemmed | Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship Study |
| title_short | Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship Study |
| title_sort | investigations on inhibitors of hedgehog signal pathway a quantitative structure activity relationship study |
| topic | QSAR Hedgehog signal pathway inhibitor cyclopamine |
| url | http://www.mdpi.com/1422-0067/12/5/3018/ |
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