Discovery of novel inhibitors of human S-adenosylmethionine decarboxylase based on in silico high-throughput screening and a non-radioactive enzymatic assay
Year: 2015
Type: article
Abstract: Natural polyamines are small polycationic molecules essential for cell growth and development, and elevated level of polyamines is positively correlated with various cancers. As a rate-limiting enzyme of the polyamine biosynthetic pathway, S-adenosylmethionine decarboxylase (AdoMetDC) has been an attractive drug target. In this report, we present the discovery of novel human AdoMetDC (hAdoMetDC) inhibitors by coupling computational and experimental tools. We constructed a reasonable computational structure model of hAdoMetDC that is compatible with general protocols for high-throughput drug screening, and used this model in in silico screening of hAdoMetDC inhibitors against a large compound library using a battery of computational tools. We also established and validated a simple, economic, and non-radioactive enzymatic assay, which can be adapted for experimental high-throughput screening of hAdoMetDC inhibitors. Finally, we obtained an hAdoMetDC inhibitor lead with a novel scaffold. This study provides both new tools and a new lead for the developing of novel hAdoMetDC inhibitors.
Source: Scientific Reports
DOI: 10.1038/srep10754
Authors: Chenzeng Liao, Yanlin Wang, Xiao Tan, Lidan Sun, Sen Liu
Institution: China Three Gorges University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W899576424