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27 factor receptors. J. Pharmacol. Exp. Ther. 295, 139–145. , Lemercier, C. and Seigneurin-Berny, D. (2001) Functional significance of histone deacetylase diversity. Curr. Opin. Genet. Dev. 11, 162–166. Marks, P. A. and Xu, W. S. (2009) Histonedeacetylase inhibitors: potential in cancer therapy. J. Cell Biochem. 107, 600–608. Somoza, J. , Skene, R. , Katz, B. , Mol, C. , Ho, J. , Jennings, A. , Buggy, J. , Sang, B. , Leahy, E. , Dougan, D. , Knuth, M. , Swanson, R. , McRee, D. E. and Tari, L. W.

The improved ligand efficiency observed for Tamiflu™ is due in part to the ethylpropoxy group, which induces a conformational change in key active-site pocket residues and participates in lipophilic interactions (24, 27). Conversion of the zwitterionic parent compound to the ethyl ester pro-drug allow the compound to be administered orally, making Tamiflu™ the first neuraminidase inhibitor used as an oral anti-influenza drug. The improved physical property profile of Tamiflu™ vs. Relenza™ translated to considerable commercial success.

J. Health Econ. 13, 282–406. 3. , Nystrom, J. , Bredberg, U. and Teger-Nilsson, A. –C. (2004) A new oral anticoagulant: the 50-year challenge. Nature Rev. Drug. Discov. 3, 649–659. 4. McCoy, A. , Grosse-Kunstleve, R. , Adams, P. , Winn, M. , Storoni, L. C. and Read, R. J. (2007) Phaser crystallographic software. J. Appl. Cryst. 40, 658–674. 5. Blundell, T. L. and Johnson, L. N. (1976) In Protein Crystallography. Academic Press, New York. 6. Stout, G. H. and Jensen, L. H. (1989) In X-ray Structure Determination: A Practical Guide.

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