TP-0413 is a novel small molecule inhibitor of the BMP pathway that has significant potential to be developed to treat anemia of cancer. Anemia of cancer is cytokine driven and results in the up-regulation of a liver hormone called hepcidin through the function of BMP receptors. Increased hepcidin levels result in the storage of iron in cellular compartments resulting in low serum iron and anemia. Anemia of cancer is a significant health issue in a majority of cancer patients and is currently only treatable by blood transfusion. As an inhibitor of BMP signaling, TP-0413 has shown promise in cell-based and animal models. TP-0413 inhibits cytokine signaling and raises serum iron and red blood cells in mouse models of anemia. Ideally, TP-0413 will be developed as an oral agent and to this end, the studies described in this proposal aim at identifying and optimizing a pharmaceutical salt form of the compound that is orally available with enhanced efficacy. Furthermore, five-day repeat dose toxicity studies will be performed in rats in preparation for choosing a dose and schedule for GLP toxicity studies. The overarching goal of this work is to develop an optimized oral agent for the treatment of anemia in cancer.
