Abstract by Theo Stoddard-Bennett
Chemistry and Biochemistry
Applying HIV Protease Inhibitors to Lower Inflammatory Hepcidin Production
Anemia, or lack of bio-available iron, affects an estimated 400 million individuals worldwide. Critical iron homeostasis within organisms is limited by the peptide regulator hepcidin with elevated expression results in anemia of inflammation. Hepcidin production can be reduced by inhibiting furin, the protease that cleaves prohepcidin to hepcidin. Our previous work has shown that two known protease inhibitors (PIs) and current HIV medications curtail inflammatory hepcidin production. This approach will reduce the financial cost of drug discovery as these medications have already been approved for human use. Though promising, clinical use of these drugs is limited due to known side-effects blocking glucose transport. However, 4 other known PIs with significantly fewer side-effects are available, but their collective effects on hepcidin production remain unknown. Preliminary simulation data has identified that these 4 HIV PIs bind at the allosteric and catalytic sites of furin. Here we examine the effects of these unstudied PIs in isolation and in combination to treat those with anemia of inflammation both in vitro and in tissue culture.