PAC-1 (University of Illinois)

PAC-1 (Procaspase-activating compound 1) is a first-in-class small molecule that directly activates procaspase-3, the inactive zymogen precursor of the executioner protease caspase-3. Procaspase-3 is frequently overexpressed in various malignancies, including melanoma, lymphoma, and neuroblastoma. PAC-1 functions by sequestering inhibitory zinc ions from the procaspase-3 safety catch domain, thereby triggering the auto-activation of the enzyme and subsequent induction of apoptosis in cancer cells. This mechanism provides a selective therapeutic window, as healthy cells typically express significantly lower levels of procaspase-3. PAC-1 is being investigated in clinical trials for the treatment of metastatic uveal melanoma (often in combination with entrectinib), glioblastoma (in combination with temozolomide), and other solid tumors.

Other names

Procaspase-activating compound 1