Lead Discovery of Type II BRAF V600E Inhibitors Targeting the Structurally Validated DFG-Out Conformation Based upon Selected Fragments
Abstract
:1. Introduction
2. Results and Discussion
3. Materials and Methods
3.1. Chemistry
3.2. Biochemical Assays
3.3. Docking
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
ATP | adenosine triphosphate |
DFG | Asp-Phe-Gly |
FDA | Food and Drug Administration |
HRD | His-Arg-Asp |
INN | International Nonproprietary Names |
PDB | Protein Data Bank |
SAR | structure-activity relationship |
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Compound | IC50 (nM) | GlideScore (kJ/mol) |
---|---|---|
SI-046 | 298 | 11.3 |
SI-008 | 685 | 10.3 |
SI-098 | >10,000 | 10.2 |
sorafenib | 263 | 12.1 |
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Zhang, Q.; Zhang, X.; You, Q. Lead Discovery of Type II BRAF V600E Inhibitors Targeting the Structurally Validated DFG-Out Conformation Based upon Selected Fragments. Molecules 2016, 21, 879. https://doi.org/10.3390/molecules21070879
Zhang Q, Zhang X, You Q. Lead Discovery of Type II BRAF V600E Inhibitors Targeting the Structurally Validated DFG-Out Conformation Based upon Selected Fragments. Molecules. 2016; 21(7):879. https://doi.org/10.3390/molecules21070879
Chicago/Turabian StyleZhang, Qingwen, Xuejin Zhang, and Qidong You. 2016. "Lead Discovery of Type II BRAF V600E Inhibitors Targeting the Structurally Validated DFG-Out Conformation Based upon Selected Fragments" Molecules 21, no. 7: 879. https://doi.org/10.3390/molecules21070879