In:
ChemMedChem, Wiley, Vol. 16, No. 16 ( 2021-08-19), p. 2515-2523
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.
Type of Medium:
Online Resource
ISSN:
1860-7179
,
1860-7187
DOI:
10.1002/cmdc.202100064
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
2209649-8
detail.hit.zdb_id:
2218496-X
SSG:
15,3
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