Molecule of the Month
October 2019
Downregulation of Nonsense-Mediated mRNA Decay (NMD)
Using Small-Molecule Inhibitors

Recently we started using small-molecule inhibitors as a tool to study mechanistic aspects of NMD and investigate potential therapeutic approaches. The molecule shown here was synthesized by Gopalsamy et al., 2012, and targets SMG1, the only known kinase in the NMD pathway.
The inhibitor leads to efficient stabilization of NMD sensitive mRNAs (right side, upper panel) and reduces the phosphorylation of UPF1 (right side, lower panel), an important step for NMD activation.

This work is carried out by Lukas Gurzeler in the group of Prof. Oliver Mühlemann.


  • A. Gopalsamy, E. M. Bennett, M. Shi, W.G. Zhang, J. Bard, K. Yu;
    "Identification of pyrimidine derivatives as hSMG-1 inhibitors "
    Bioorg. Med. Chem. Lett., 2012, 22(21), 6636-6641; doi:10.1016/j.bmcl.2012.08.107.