An AlphaLISA screen opens the ISG15–UBA7 interaction to inhibitor hunting
- ISG15 and its E1 enzyme UBA7 drive ISGylation, a pathway linked to treatment resistance in cancer, yet no inhibitors exist.
- The authors built an AlphaLISA assay for the ISG15–UBA7 interaction with strong robustness metrics for high-throughput use.
- A pilot screen of a small library gave a handful of hits, two of which also reduced ISGylation in cells.
💡 Points
This is a pilot on under a thousand compounds, so the hits are starting points, not leads. What matters is that a protein-protein interaction between a ubiquitin-like modifier and its E1 now has a screenable format. I'd run it against a real diversity set and counter-screen AlphaLISA interferers hard.