Journal of Medicinal Chemistry
Article
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compounds, dose−response data on fragment hits 2 and 3, and
table on methods used for PARP1 activity assays. This material
Accession Codes
The crystal structures of compounds 2, 3, 11, 14, 15, 16, and
17 in complex with TNKS2 have been deposited with the
RCSB Protein Data Bank under the accession codes 4JIZ,
3W5I, 41UE, 4J21, 4J22, 4J3L, 4J3M.
(8) Shultz, M. D.; Kirby, C. A.; Stams, T.; Chin, D. N.; Blank, J.;
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ylsulfanylmethyl)-3-phenyl-[1,2,4]oxadiazoles: antagonists of the Wnt
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AUTHOR INFORMATION
Corresponding Author
■
Author Contributions
(9) Chen, B.; Dodge, M. E.; Tang, W.; Lu, J.; Ma, Z.; Fan, C.-W.;
Wei, S.; Hao, W.; Kilgore, J.; Williams, N. S.; Roth, M. G.; Amatruda, J.
F.; Chen, C.; Lum, L. Small molecule-mediated disruption of Wnt-
dependent signaling in tissue regeneration and cancer. Nat. Chem. Biol.
2009, 5, 100−107.
∥E.A.L. and A.J. contributed equally to this work.
Notes
The authors declare no competing financial interest.
(10) Peterson, R. T. Drug discovery: propping up a destructive
regime. Nature 2009, 461, 599−600.
ACKNOWLEDGMENTS
■
Portions of this research were carried out at the National
Synchrotron Radiation Research Center, a national user facility
supported by the National Science Council of Taiwan, Republic
of China. The Synchrotron Radiation Protein Crystallography
Facility is supported by the National Research Program for
Genomic Medicine. This research was also undertaken on the
MX1 beamline at the Australian Synchrotron, Victoria,
Australia. We thank the beamline staff at both the synchrotrons
for all their help during data collection. This work was
supported by funding from a principal investigator start-up
grant from Nanyang Technological University, the National
Research Foundation (Grant NRF-CRP4-2008-02), and the
Biomedical Research Council.
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̈
selective inhibition of human tankyrases. J. Med. Chem. 2012, 55,
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Copsey, L.; Cranston, A.; Dillon, K. J.; Drzewiecki, J.; Garman, S.;
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ABBREVATIONS USED
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FBLD, fragment-based ligand design; SPR, surface plasmon
resonance; DSF, differential scanning fluorometry; NAD+,
nicotinamide adenine dinucleotide; PARP, poly(ADP-ribose)
polymerase; TNKS, tankyrase (TRF1-interacting, ankyrin-
related ADP-ribose polymerase)
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