Screening of Inhibitors Targeting Heat Shock Protein 47 Involved in the Development of Idiopathic Pulmonary Fibrosis

Heat shock protein 47 (HSP47), a collagen‐specific molecular chaperone, is causally related to fibrotic diseases, including idiopathic pulmonary fibrosis. The identification of Compounds that interfere with the HSP47‐collagen interaction is essential for the development of relevant therapeutics. Herein, we prepared human HSP47 as a soluble fusion protein expressed in E. coli and established an assay system for HSP47 inhibitor screening. We screened a natural and synthetic Compound library established at Nagasaki University. Among 1023 Compounds, 13 exhibited inhibitory activity against human HSP47, of which three inhibited its function in a dose‐dependent manner. Epigallocatechin‐3‐O‐gallate, one of these three Compounds, is a typical polyphenol Compound derived from tea leaves. Structurally related Compounds were synthesized and examined for their activity, revealing a hydroxyl group at A‐ring position 5 as important for its activity. The present findings provide valuable insight for the development of natural product‐derived therapeutics for fibrotic diseases, including idiopathic pulmonary fibrosis. Combating IPF: Human heat‐shock protein 47 (HSP47) is a novel therapeutic target for fibrotic diseases. A screening system consisting of a recombinant human HSP47 and a natural Compound library was developed to identify and select for HSP47 inhibitors. One of the hit Compounds was epicallocathechin‐3‐O‐gallate, and its derivatives were examined to determine the relationship between structure and activity.