Idiopathic pulmonary fibrosis (IPF) is the most fatal interstitial lung disease, with high mortality but with few good treatment options. IPF is suspected to develop from poorly defined, repeated alveolar injuries that cause increased secretion of extracellular matrix (ECM) proteins and collagen production that result in the scarring characteristic of IPF. New FDA approved treatments do not stop disease progression and have considerable side effects. We have identified matrix and matrix-processing enzymes as novel drug targets for IPF. One such protein, FK506-binding protein 10 (FKBP10), has been shown to play a pivotal role during these processes. Importantly, loss of FKBP10 has been shown to correlate with attenuated collagen production and diminished collagen 1 cross-linking. Herein, we propose to make a library of non-immunosuppressant inhibitors of FKBP10 followed by in vivo characterization of the efficacy of the new inhibitors.
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with a 5-year survival rate of 30 to 50% with few good treatment options available. Increased secretion of matrix proteins and collagen production causing thickening of the lung tissues play a significant role in the pathology. We have developed a strategy to target IPF by inhibiting FKBP10.