AI Article Synopsis
- Platelet-derived growth factor (PDGF) is involved in cell growth and movement but can cause health issues like cancer and atherosclerosis when overactivated.
- This study aimed to find new inhibitors of PDGF-B using virtual screening methods, utilizing techniques like molecular docking and simulation based on an existing anti-PDGF-B antibody's structure.
- In laboratory tests, two compounds showed significant activity, suggesting a potential framework for developing more anti-PDGF-B agents from large chemical libraries.
Article Abstract
Platelet-derived growth factor (PDGF) is a family of growth factors with mitogenic and chemotactic activity. However, uncontrolled and overactivated PDGF signaling has been implicated in a variety of diseases, such as cancers and atherosclerosis. In this context, inhibition of PDGF-PDGFR signaling is of paramount importance in progression of such diseases. The purpose of the current study was to identify novel PDGF-B inhibitors using virtual screening methods. To this end, a combination of molecular modeling techniques such as molecular docking and dynamics simulation, as well as drug likeness filtering criteria, was applied to select anti-PDGF peptidomimetic candidates based on crystallography solved structure of an anti-PDGF-B monoclonal antibody named, MOR8457. In vitro biological assays of the selected compounds revealed two of them being active at micromolar IC concentrations. The presented work can provide a framework for systematic peptidomimetic identification for anti-PDGF-B agents from large chemical libraries.
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| http://dx.doi.org/10.1016/j.bioorg.2019.103374 | DOI Listing |
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