Pumping iron

A new small molecule for iron deficiency diseases

A natural compound from the Japanese Hinoki tree may hold the answer to iron transport diseases treated inadequately by phlebotomy, chelation therapy or dietary supplements. In Science last month, a University of Illinois-led group reported that the small molecule hinokitiol can replace defective iron transport proteins, and move iron in and out of cells.

The team plans to test the molecule in the clinic, and is generating derivatives both to optimize and better understand its properties.

And beyond the study’s therapeutic implications, the authors believe their screening strategy could become a general platform for discovering ion transport modulators.

Movement of iron around the body involves a complex system of active and passive transporters with varied expression patterns, subcellular locations and directional transport. Iron absorbed from food is transported across the gut epithelium to blood, where it is moved by plasma proteins to the bone marrow for new blood cell production and into other organs for a variety of metabolic roles.

Although there are at least 25 genetic diseases associated with defects in iron transport or metabolism, no therapies in the clinic are capable of substituting for any of the three primary human active iron transporters - SLC11A2, SLC40A1 and mitoferrin.

Mutations in SLC40A1 cause the iron overload disorder hemochromatosis type 4; mutations in SLC11A2 have

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