biostudies-literatureUnknown12(3)Stefanovic BFlorida Department of HealthFibrosis is a major medical problem caused by excessive synthesis of the extracellular matrix, composed predominantly of type I collagen, in various tissues. There are no approved antifibrotic drugs, and the major obstacle in finding clinically relevant compounds is the lack of specificity of current experimental drugs for type I collagen. Here we describe the discovery of a lead compound that specifically inhibited secretion of type I collagen by fibroblasts in culture at IC₅₀ = 4.5 μM. The inhibition was specific for type I collagen, because secretion of fibronectin was not affected. In vitro, the compound inhibited binding of LARP6, the master regulator of translation of type I collagen mRNAs, to the 5' stem-loop sequence element which regulates their translation. Because binACS medicinal chemistry letters477-484https://www.ebi.ac.uk/biostudies/studies/S-EPMC7958148biostudies-literatureDiscovery of a Lead Compound for Specific Inhibition of Type I Collagen Production in Fibrosis.PMC7958148Stefanovic BNefzi AMichaels HAfalseDiscovery of a Lead Compound for Specific Inhibition of Type I Collagen Production in Fibrosis.Fibrosis is a major medical problem caused by excessive synthesis of the extracellular matrix, composed predominantly of type I collagen, in various tissues. There are no approved antifibrotic drugs, and the major obstacle in finding clinically relevant compounds is the lack of specificity of current experimental drugs for type I collagen. Here we describe the discovery of a lead compound that specifically inhibited secretion of type I collagen by fibroblasts in culture at IC₅₀ = 4.5 μM. The inhibition was specific for type I collagen, because secretion of fibronectin was not affected. In vitro, the compound inhibited binding of LARP6, the master regulator of translation of type I collagen mRNAs, to the 5' stem-loop sequence element which regulates their translation. Because bin2021-01-01T00:00:00Z2021 Mar2025-04-04T20:50:22.435Z2025-04-04T20:50:22.435ZS-EPMC79581483373807510.1021/acsmedchemlett.1c00006