FRET assay for G3BP1 and G3BP2 inhibitors (SJ-19-0043)

St. Jude Reference #SJ-19-0043


Researchers at St. Jude have developed a fluorescence resonance energy transfer (FRET) assay which can be used in high throughput screens to identify small molecule inhibitors of G3BP1 and G3BP2. Identified compounds may be used to inhibit G3BP function, including modulation of stress granule assembly.  These compounds are expected to be therapeutically beneficial for a variety of diseases, including neurodegenerative diseases, viral infection, autoimmune disorders and tumorigenesis.

Inhibitors of stress granule assembly have been previously identified, which target regulators of translation or upstream stress responses; however, there are neither inhibitors of G3BP(1or2) nor are there assays designed to identify such inhibitors. Researchers at St. Jude have identified G3BP1 and G3BP2 as uniquely important scaffolds for stress granule assembly, revealing the importance of targeting this molecule directly. Moreover, G3BP1 is involved in coordinating other important, disease-relevant activities that are independent of stress granule assembly, such as viral replication, cGAS activation, regulation of cancer metastasis and more, highlighting the need for direct inhibitors of this molecule. The ability of the assay to discover and develop these inhibitors should prove very successful.


Small molecule, G3BP1 inhibitor, modulation of stress granule assembly, neurodegenerative diseases, viral infection, autoimmune disorders, cancer, tumorigenesis.

Granted patents or published applications

International PCT patent application

Related scientific references

Peiguo Yang, Cécile Mathieu, Regina-Maria Kolaitis, Peipei Zhang, James Messing, Ugur Yurtsever, Zemin Yang, Jinjun Wu, Yuxin Li, Qingfei Pan, Jiyang Yu, Erik W. Martin, Tanja Mittag, Hong Joo Kim, J. Paul Taylor, G3BP1 Is a Tunable Switch that Triggers Phase Separation to Assemble Stress Granules, Cell, Volume 181, Issue 2, 16 April 2020, Pages 306-324.e28

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