Int. J. Mol. Sci. 2011, 12(5), 3018-3033; doi:10.3390/ijms12053018
Article

Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship Study

1,†email, 1,†email, 2email, 2,* email and 1,* email
1 Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China 2 Department of Natural Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 14 March 2011; in revised form: 20 April 2011 / Accepted: 28 April 2011 / Published: 11 May 2011
PDF Full-text Download PDF Full-Text [317 KB, uploaded 11 May 2011 14:08 CEST]
Abstract: 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.
Keywords: QSAR; Hedgehog signal pathway; inhibitor; cyclopamine

Supplementary Files

Article Statistics

Load and display the download statistics.

Citations to this Article

Cite This Article

MDPI and ACS Style

Zhu, R.; Liu, Q.; Tang, J.; Li, H.; Cao, Z. Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship Study. Int. J. Mol. Sci. 2011, 12, 3018-3033.

AMA Style

Zhu R, Liu Q, Tang J, Li H, Cao Z. Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship Study. International Journal of Molecular Sciences. 2011; 12(5):3018-3033.

Chicago/Turabian Style

Zhu, Ruixin; Liu, Qi; Tang, Jian; Li, Huiliang; Cao, Zhiwei. 2011. "Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship Study." Int. J. Mol. Sci. 12, no. 5: 3018-3033.

Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert