Identification of small molecule inhibitors that distinguish between non-transferrin bound Iron uptake and transferrin-mediated iron transport

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Abstract

Chemical genetics is an emerging field that takes advantage of combinatorial chemical and small molecule libraries to dissect complex biological processes. Here we establish a fluorescence-based assay to screen for inhibitors of iron uptake by mammalian cells. Using this approach, we screened the National Cancer Institute's Diversity Set library for inhibitors of non-transferrin bound iron uptake. This screen identified 10 novel small molecule inhibitors of iron transport with IC50 values that ranged from 5 to 30 μM. Of these ten compounds, only two blocked uptake of iron mediated by transferrin. Thus, this study characterizes the first small molecule inhibitors that distinguish between different pathways of iron transport.

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Brown, J. X., Buckett, P. D., & Wessling-Resnick, M. (2004). Identification of small molecule inhibitors that distinguish between non-transferrin bound Iron uptake and transferrin-mediated iron transport. Chemistry and Biology, 11(3), 407–416. https://doi.org/10.1016/j.chembiol.2004.02.016

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