3D-QSAR and docking studies on pyridopyrazinones as BRAF inhibitors

BRAF has become an important and exciting therapeutic target toward human cancer. 3D-QSAR and docking studies were performed to explore the interaction of the BRAF with a series of pyridopyrazinones. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analys...

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Bibliographic Details
Published inMedicinal chemistry research Vol. 20; no. 8; pp. 1298 - 1317
Main Authors Ai, Yong, Wang, Shao-Teng, Tang, Chu, Sun, Ping-Hua, Song, Fa-Jun
Format Journal Article
LanguageEnglish
Published New York Springer-Verlag 01.11.2011
Subjects
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Original Research
Pharmacology/Toxicology
3D-QSAR
Pyridopyrazinones
Docking
BRAF
CoMFA
CoMSIA
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Summary:BRAF has become an important and exciting therapeutic target toward human cancer. 3D-QSAR and docking studies were performed to explore the interaction of the BRAF with a series of pyridopyrazinones. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were carried out in terms of their potential for predictability. The CoMFA and CoMSIA models using 71 compounds in the training set gave r cv 2 values of 0.567 and 0.662, r 2 values of 0.900 and 0.907, respectively. The 3D contour maps generated by the CoMFA and CoMSIA models were used to identify the key structural requirements responsible for the biological activity. Molecular docking was applied to explore the binding mode between the ligands and the receptor. The information obtained by 3D-QSAR models may be useful to design novel potential BRAF inhibitors.
ISSN:1054-2523
1554-8120
DOI:10.1007/s00044-010-9468-1