Discovery of Potent STT3A/B Inhibitors and Assessment of Their Multipathogen Antiviral Potential and Safety
- J Med Chem. 2024 Aug 22;67(16):14586-14608. doi: 10.1021/acs.jmedchem.4c01402.
- 1. GSK, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States.
- 2. Vir Biotechnology, Inc., 1800 Owens St., San Francisco, California 94158, United States.
- 3. Cellzome GmbH, a GSK company, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
In the aftermath of the COVID-19 pandemic, opportunities to modulate biological pathways common to the lifecycles of viruses need to be carefully considered. N-linked glycosylation in humans is mediated exclusively by the oligosaccharyltransferase complex and is frequently hijacked by viruses to facilitate Infection. As such, STT3A/B, the catalytic domain of the OST complex, became an intriguing drug target with broad-spectrum Antiviral potential. However, due to the critical role N-linked glycosylation plays in a number of fundamental human processes, the toxicological ramifications of STT3A/B inhibition required attention commensurate to that given to Antiviral efficacy. Herein, we describe how known STT3A/B inhibitor NGI-1 inspired the discovery of superior tool compounds which were evaluated in in vitro efficacy and translational safety (e.g., CNS, cardiovascular, liver) studies. The described learnings will appeal to those interested in the therapeutic utility of modulating N-linked glycosylation as well as the broader scientific community.
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Cat. No.Product NameDescriptionTargetResearch Area
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target: Virus Protease