The best trivalent PROTAC designed by the researchers proved to be remarkably more potent than their bivalent predecessor compounds, showing in cellular studies stronger anti-cancer activity at a much lower dose and improved pharmacological responses over a wider dose range. However, new research carried out by Dundee’s Centre for Targeted Protein Degradation (CeTPD) in collaboration with biotechnology company Promega broke away from this conventional design and showed that degraders can be significantly improved by making them trivalent, i.e. PROTACs are conventionally small molecules designed with two heads, called bivalent or heterobifunctional compounds. The first compounds in this class, termed Proteolysis-targeting chimeras (PROTACs), are being trialed as candidate medicines against various cancers and progressing through clinical trials. This type of drug may show a greater response even at lower doses, and it is more precise with potentially reduced side effects and disease resistance. This system is applicable to diverse therapeutic areas including oncology, inflammation, dermatology, immunology, and respiratory diseases.ĭegrading a target protein offers several advantages over traditional inhibitors. It involves co-opting the cell’s natural disposal systems to also remove disease-causing proteins. Targeted protein degradation is an area of chemical biology that is revolutionizing drug discovery. The research is published today in Nature Chemical Biology. This discovery opens new possibilities in a field that is revolutionizing drug discovery for cancer and other targets. Researchers from the University of Dundee and Promega Corporation have shown how a “three-headed hydra” significantly improves efficacy in targeted protein degradation.
0 Comments
Leave a Reply. |