Identification of Putative Non-Substrate-Based XT-I Inhibitors by Natural Product Library Screening.

ABSTRACT: Fibroproliferative diseases are characterized by excessive accumulation of extracellular matrix (ECM) components leading to organ dysfunction. This process is characterized by an increase in myofibroblast content and enzyme activity of xylosyltransferase-I (XT-I), the initial enzyme in proteoglycan (PG) biosynthesis. Therefore, the inhibition of XT-I could be a promising treatment for fibrosis. We used a natural product-inspired compound library to identify non-substrate-based inhibitors of human XT-I by UPLC-MS/MS. We combined this cell-free approach with virtual and molecular biological analyses to confirm and prioritize the inhibitory potential of the compounds identified. The characterization for compound potency in TGF-β1-driven XYLT1 transcription regulation in primary dermal

SUBMITTER: Ly TD 

PROVIDER: S-EPMC7589200 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature