pubs.acs.org/acsmedchemlett
AUTHOR INFORMATION
(13) Tao, P.; Fisher, J. F.; Mobashery, S.; Schlegel, H. B. DFTstudies
of the ring-opening mechanism of SB-3CT, a potent inhibitor
of matrix metalloproteinase 2. Org. Lett. 2009, 11, 2559–
2562.
Corresponding Author: *M.C.: phone, (574) 631-2965; fax,
(574) 631-6652; e-mail, mchang@nd.edu. S.M.: phone, (574) 631-
2933; fax, (574)631-6652; e-mail, mobashery@nd.edu.
(14) Tao, P.; Fisher, J.; Shi, Q.; Vreven, T.; Mobashery, S.; Schlgel,
H. B. Matrix metalloproteinase 2 (MMP2) inhibition: QM/MM
studies of the inhibition mechanism of SB-3CTand its analog.
Biochemistry 2009, 48, 9839–9847.
Author Contributions: † Authors contributed equally to this
work.
(15) Tao, P.; Fisher, J. F.; Shi, Q.; Mobashery, S.; Schlegel, H. B.
Matrix metalloproteinase 2 (MMP2) inhibition: DFTand QM/
MM studies of the deprotonation initiated ring opening
reaction of sulfoxide analog of SB-3CT. J. Phys. Chem. 2010,
114, 1030–1037.
Funding Sources: This research was supported by a grant from
the National Institutes of Health (CA122417).
(16) Lee, M.; Villegas-Estrada, A.; Celenza, G.; Boggess, B.; Toth,
M.; Kreitinger, G.; Forbes, C.; Fridman, R.; Mobashery, S.;
Chang, M. Metabolism of a highly selective gelatinase inhi-
bitor generates active metabolite. Chem. Biol. Drug Des. 2007,
70, 371–382.
(17) Lee, M.; Celenza, G.; Boggess, B.; Blase, J.; Shi, Q.; Toth, M.;
Bernardo, M. M.; Wolter, W. R.; Suckow, M. A.; Hesek, D.; Noll,
B. C.; Fridman, R.; Mobashery, S.; Chang, M. A potent
gelatinase inhibitor with anti-tumor-invasive activity and its
metabolic disposition. Chem. Biol. Drug Des. 2009, 73, 189–
202.
ACKNOWLEDGMENT R.T.S. acknowledges support from the
University of Notre Dame College of Science Summer Undergrad-
uate Research Fellowship. L.I.L. is a Pew Latin American Fellow in
the Biomedical Sciences, supported by The Pew Charitable Trusts.
The opinions expressed are those of the authors and do not
necessarily reflect the views of The Pew Charitable Trusts. We thank
the Mass Spectrometry & Proteomics Facility (Bill Boggess, Nonka
Sevova, and Michelle Joyce), the University of Notre Dame, which
is supported by Grant CHE-0741793 from the National Science
Foundation.
(18) Ikejiri, M.; Bernardo, M. M.; Bonfil, R. D.; Toth, M.; Chang, M.;
Fridman, R.; Mobashery, S. Potent mechanism-based inhibi-
tors for matrix metalloproteinases. J. Biol. Chem. 2005, 280,
33992–34002.
(19) Bernardo, M. M.; Brown, S.; Li, Z. H.; Fridman, R.; Mobashery,
S. Design, synthesis and characterization of potent, slow-
binding inhibitors that are selective for gelatinases. J. Biol.
Chem. 2002, 277, 11201–11207.
(20) Lee, M.; Bernardo, M. M.; Meroueh, S. O.; Brown, S.; Fridman,
R.; Mobashery, S. Synthesis of chiral 2-(4-Phenoxyphenyl-
sulfonylmethyl)-thiiranes as selective gelatinase inhibitors.
Org. Lett. 2005, 7, 4463–4465.
(21) Lu, C.; Li, P.; Gallegos, R.; Uttamsingh, V.; Xia, C. Q.; Miwa,
G. T.; Balani, S. K.; Gan, L.-S. Comparison of intrinsic clear-
ance in liver microsomes and hepatocytes from rats and
humans: evaluation of free fraction and uptake in hepato-
cytes. Drug Metab. Dispos. 2006, 34, 1600–1605.
(22) Toth, M.; Bernardo, M. M.; Gervasi, D. C.; Soloway, P. D.;
Wang, Z.; Bigg, H. F.; Overall, C. M.; DeClerk, Y. A.; Tschesche,
H.; Cher, M. L.; Brown, S.; Mobashery, S.; Fridman, R. Tissue
inhibitor of metalloproteinase (TIMP)-2 acts synergistically
with synthetic matrix metalloproteinase (MMP) inhibitors
but not with TIMP-4 to enhance the (membrane type 1)-
MMP-dependent activation of pro-MMP-2. J. Biol. Chem.
2000, 275, 41415–41423.
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DOI: 10.1021/ml100254e ACS Med. Chem. Lett. 2011, 2, 177–181
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