SJB3-019A

SJB3-019A is a small molecule inhibitor of Ubiquitin-specific protease 1 (USP1), a deubiquitinating enzyme that plays a critical role in DNA damage response and cell cycle regulation. In H3K27M-mutant diffuse midline gliomas (DMGs), USP1 is upregulated and contributes to tumor cell proliferation and stemness. SJB3-019A treatment has been shown to reduce DMG cell viability, induce apoptosis, and downregulate key proteins such as ID1, SOX2, and Checkpoint Kinase 1 (CHEK1). Furthermore, SJB3-019A acts as a radiosensitizer, enhancing the lethal effects of ionizing radiation by impairing DNA repair mechanisms and checkpoint fidelity, making it a promising candidate for combination therapy in pediatric brain tumors.