Discovery of a Lead Compound for Specific Inhibition of Type I Collagen Production in Fibrosis.

ABSTRACT: 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 bin

SUBMITTER: Stefanovic B 

PROVIDER: S-EPMC7958148 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature