Human kallikrein 6 inhibitors with a para-amidobenzylanmine P1 group identified through virtual screening
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Acknowledgments
Authors would like to thank Drs. Sukanthini Thurairatnam, Larry McLean, Isabelle Morize, and David Lythgoe for support and to thank Drs. Sheng-Yuh Tang, Dirk Friedrich, and Henning Steinhagen for helpful discussions.
References and notes (39)
- et al.
Trends Endocrinol. Metabol.
(2000) - et al.
Biochim. Biophys. Acta Rev. Cancer
(2007) - et al.
Clin. Biochem.
(2000) - et al.
Clin. Chim. Acta
(2003) - et al.
J. Biol. Chem.
(2007) - et al.
J. Mol. Biol.
(1998) - et al.
J. Mol. Biol.
(2000) - et al.
Bioorg. Med. Chem. Lett.
(2000) - et al.
Bioorg. Med. Chem. Lett.
(2006) - et al.
Chem. Biol. (Cambridge, MA, United States)
(2008)
Bioorg. Med. Chem.
Biochem. Biophys. Res. Commun.
J. Biol. Chem.
Biol. Chem.
Endocr. Rev.
Biol. Chem.
Cell. Mol. Life Sci.
Handbook of Proteolytic Enzymes; 2nd ed
Elsevier Academic Press
Cancer Res.
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