MedChemComm
Research Article
Table 2 Results from 96 h MTT assay using Raji Burkitt B-cell lymphoma.
All compounds were nontoxic over 96 h at 10 μM to the control MCT1-
deficient breast cancer cell line MDA-MB-231 using an MTT assay, indi-
cating that selective cytotoxicity is driven by MCT1 inhibition
Acknowledgements
Financial support was provided by the Bankhead-Coley New
Investigator Grant 1BN01 from the Florida Biomedical Re-
search Program, by grants U54MH084512, CA154739 and P30
CA076292-14 from the National Cancer Institute/National In-
stitutes of Health, and by financial support from the State of
Florida given to Scripps Florida and to the Moffitt Cancer
Center. We thank Dr. Xiangming Kong, NMR core facility
manager at Scripps Florida, for assistance with NMR tech-
niques. We also thank Dr. Kristen E. N. Scott for review of the
biological data and for assistance in the construction of
figures.
X =
X =
EC50 (nM)
5
EC50 (nM)
11
5
7
60
55
1000
690
Notes and references
36
38
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Conclusions
Appending Gln and Tyr residues to an MCT1 inhibitor, simi-
lar to their use in contrast imaging agents, consistently en-
hanced toxicity vs. Raji cells, which express MCT1 and the
amino acid transporters LAT1 and Asct2. The enhanced cyto-
toxicity likely arises from facilitated transport into Raji cells.
Future work includes linker and transporter recognition ele-
ment optimization, MCT inhibitor optimization and the
application of such conjugation strategies to other classes of
anti-tumour agents.
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