title: Identification of small molecule inhibitors that distinguish between non-transferrin bound iron uptake and transferrin-mediated iron transport.
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 IC(50) values that ranged from 5 to 30 microM. 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.
authors.affiliation: Harvard School of Public Health, Department of Genetics and Complex Diseases, 665 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Jing Xu
authors.initials: JX
authors.lastname: Brown
authors.forename: Peter D
authors.initials: PD
authors.lastname: Buckett
authors.forename: Marianne
authors.initials: M
authors.lastname: Wessling-Resnick
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007501:Iron / Q000378:metabolism*; D015394:Molecular Structure; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D014168:Transferrin / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations; D014168:Transferrin; D007501:Iron