Restoration of PP2A AαB56αC trimer formation by RPT04402 molecular glue in high-grade uterine cancer.

RPT04402 molecular glue restores PP2A trimer formation and induces tumor regression in high-grade uterine cancer models with PPP2R1A mutations.

• Why it matters: High-grade endometrial cancers with PPP2R1A mutations are highly aggressive, and current therapies lack targeted options for these driver mutations.
• What they did: Researchers identified RPT04402 through a small-molecule library designed to fit the PP2A Aα/B56α/C interface, promoting heterotrimerization in mutant scaffolds, and tested its effects in mice with mutant cell lines and patient-derived xenografts.
• The result: RPT04402 treatment extended median survival and caused tumor regressions in mice, with activity dependent on B56α, suggesting PP2A molecular glues could be a promising therapy for PPP2R1A-mutant uterine cancer.