PAC-1 (Procaspase activating compound 1) is an anti-cancer compound that works against a multitude of cancer types. PAC-1 works by binding zinc ions that inactivate the activity of procaspase-3.
Procaspase-3 is the zymogen form of caspase-3. High expression of procaspase-3 is found in a variety of cancer types including brain, breast, lung and colon cancers. Because of its high expression in some rare carcinoma, procaspase-3 is an excellent anti-cancer target. Caspase-3 is needed for cells to undergo apoptosis, or programmed cell-death. Procaspase-3 is activated to caspase-3 by caspase-8 or caspase-9, after the apoptosis signaling cascade is begun.
One atom that inhibits the activation of procaspase-3 to caspase-3 is endogenous zinc found in cells. PAC-1 selectively chelates to zinc ions bound to procaspase-3. With PAC-1 chelating to zinc ions, pro-caspase-3 is activated to caspase-3 and cancerous cells can undergo apoptosis. PAC-1 has recently been used in a phase I clinical trial for efficacy against glioblastoma. PAC-1 is an attractive molecule against this cancer type due to its ability to cross the blood-brain barrier in the body.
PAC-1 also acts synergistically with some common cancer treatments. It has been shown that PAC-1 can act synergistically with doxorubicin, both in vitro and in vivo. Experiments in canines showed that both canine lymphoma and canine osteosarcoma tumors regressed with combined doxorubicin/PAC-1 treatment.
PAC-1 is available now from LKT Laboratories, Inc.
1. Putt, K.S., Chen, G.W., Pearson, J. M. et al. “Small-molecule activation of procaspase-3 to caspase-3 as a personalized anticancer strategy.” Nature Chem. Biol. 2006 Oct; 2(10): 543-550. Doi:10.1038/nchembio814.
2. Botham, R. C., Roth, H. S., Book, A.P. et al. “Small-Molecule Procaspase-3 Activation Sensitizes Cancer to Treatment with Diverse Chemotherapeutics.” ACS Cent. Sci. 2016 Aug 24; 2(8):545-59. Doi: 10.1021/acscentsci.6b00165.