Screening of Inhibitors Targeting Heat Shock Protein 47 Involved in the Development of Idiopathic Pulmonary Fibrosis.
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| Abstract |
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.
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| Authors | Daisuke Okuno, Noriho Sakamoto, Mohammed S O Tagod, Yoshiko Akiyama, Sakiko Moriyama, Takuto Miyamura, Atsuko Hara, Takashi Kido, Hiroshi Ishimoto, Yuji Ishimatsu, Takashi Tanaka, Jun Ishihara, Kohsuke Takeda, Yoshimasa Tanaka, Hiroshi Mukae |
| Journal | ChemMedChem (ChemMedChem) Vol. 16 Issue 16 Pg. 2515-2523 (08 19 2021) ISSN: 1860-7187 [Electronic] Germany |
| PMID | 33890415 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © 2021 Wiley-VCH GmbH. |
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