B32B3

B32B3 is a small molecule inhibitor of DDB1- and CUL4-associated factor 1 (DCAF1). It was identified as a therapeutic agent that stabilizes Z-DNA binding protein 1 (ZBP1) by preventing its DCAF1-mediated ubiquitination and subsequent proteasomal degradation. In the context of ovarian cancer, B32B3 works within the DAPK3-DCAF1 signaling axis to restore ZBP1 levels, which are often reduced in tumors and correlate with poor survival. By stabilizing ZBP1, B32B3 reactivates innate immune signaling and promotes PANoptosis—a coordinated cell death pathway involving pyroptosis, apoptosis, and necroptosis. This process induces immunogenic cell death and enhances anti-tumor immune responses. B32B3 has demonstrated efficacy in preclinical models of chemotherapy-resistant ovarian cancer, particularly when used in combination with Z-nucleic acid (Z-NA) activators such as CBL0137.