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Ni et al.
the reason that de novo drug design techniques in practice
are not as widely spread as virtual screening techniques. One
of the most severe limitations is that a majority number of
candidates produced by de novo drug design methods are
hard to be synthesized. Great efforts have been made in
LigBuilder 2.0 to overcome these limitations. In the present
study, we have successfully used LigBuiler2.0 to design
highly potent CypA inhibitors. We are expecting more
successful stories of drug design from scratch using de novo
design programs like LigBuilder 2.0.
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Acknowledgment. We gratefully acknowledge Professor
Wei Wang (University of New Mexico) for revising manuscript,
and the financial support from the National Natural Science
Foundation of China (grant 90813005), the 863 Hi-Tech Pro-
gram of China (grant 2006AA020400, 2006AA02Z337, 2007-
AA02Z147), the China 111 Project (grant B07023), Shanghai
Rising-Star Program (A type, grant 07QA14013), and Shanghai
Pujiang Program (D type, grant PJ200700247).
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Xu, Q.; Liu, H.; Nan, F.; Shen, J.; Bai, D.; Chen, K.; Shen, X.;
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cyclophilin A inhibitor shows highly inhibitory activity against
mouse spleen cell proliferation. Bioorg. Med. Chem. 2006, 14, 5527–
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Shen, X.; Jiang, H. Strategy for discovering chemical inhibitors
of human cyclophilin A: focused library design, virtual screening,
chemical synthesis and bioassay. J. Comb. Chem. 2006, 8, 326–337.
(18) Wang, F.; Chen, J.; Liu, X.; Shen, X.; He, X.; Jiang, H.; Bai, D.
Synthesis and peptidyl-prolyl isomerase inhibitory activity of
quinoxalines as ligands of cyclophilin A. Chem. Pharm. Bull.
2006, 54, 372–376.
(19) Wu, Y.; Belyakov, S.; Choi, C.; Limburg, D.; Thomas, B. E., IV;
Vaal, M.; Wei, L.; Wilkinson, D. E.; Holmes, A.; Fuller, M.;
McCormick, J.; Connolly, M.; Moeller, T.; Steiner, J.; Hamilton,
G. S. Synthesis and biological evaluation of non-peptidic cyclo-
philin ligands. J. Med. Chem. 2003, 46, 1112–1115.
(20) Guichou, J. F.; Viaud, J.; Mettling, C.; Subra, G.; Lin, Y. L.;
Chavanieu, A. Structure-based design, synthesis, and biological
evaluation of novel inhibitors of human cyclophilin A. J. Med.
Chem. 2006, 49, 900–910.
Supporting Information Available: General information for
chemical agents and analytical measurements, brief introduc-
tion of the LigBuilder 2.0, chemical structures of top 98
molecules, LigBuilder 2.0 predicted binding affinities of synthe-
sized compounds, detailed synthetic procedures and related
spectroscopic data for the designed compounds 1-3, HPLC
reports for the purity check of the active compounds 1-3,
and bioassay method for determining the inhibitory activity.
This material is available free of charge via the Internet at http://
pubs.acs.org.
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