Molecular glue RPT04402 restores PP2A trimer assembly in high-grade uterine cancer
- The paper describes RPT04402, a molecular glue that restores formation of the PP2A AαB56αC heterotrimer in high-grade uterine cancer.
- Recurrent PPP2R1A scaffold mutations in these tumors impair holoenzyme assembly, which the glue is designed to rescue.
- Company reports describe regressions in preclinical PP2A-mutant models and a license to SpringWorks; this summary rests on the title and secondary sources, not the full text.
💡 Points
Phosphatases are famously hard to drug, so a glue that rebuilds a specific heterotrimer rather than inhibiting an active site is a smart route around that. Here the mutation defines both the patient population and the mechanism, a tidy match. I'd watch how selective it is among the many PP2A B-subunit complexes, since activating the wrong ones is the obvious tolerability worry.