A dual MYC and GSPT1 protein degrader for MYC-driven hematologic malignancies.

GT19630, a dual MYC/GSPT1 degrader, shows low-nanomolar antiproliferative and apoptotic activity across leukemia and lymphoma cell lines and primary samples, including TP53-mutant cases.

• Why it matters: MYC is a key driver in hematologic malignancies, but direct MYC targeting has not yet succeeded, leaving a gap for effective therapies, including for therapy-resistant disease.
• What they did: The study developed GT19630 to bind MYC and GSPT1, then tested its effects on translation control, integrated stress response, oxidative phosphorylation/TCA activity, and apoptosis in vitro and in vivo.
• The result: GT19630 is highly active in vivo in therapy-resistant Burkitt lymphoma, AML, and multiple myeloma models, is more cytotoxic to CD34+ AML blasts than normal HSPCs, and restores venetoclax sensitivity while prolonging survival.

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