The investigational compound S63845, a myeloid cell leukemia 1 (MCL1) inhibitor, was shown to potently kill MCL1-dependent cancer cells, including multiple myeloma, leukemia, and lymphoma cells, according to results from a preclinical study published in Nature.
“MCL1 is important for many cancers because it is a pro-survival protein that allows the cancerous cells to evade the process of programmed cell death that normally removes cancer cells from the body,” Guillaume Lessene, PhD, associate professor at the Walter and Eliza Hall Institute of Medical Research in Australia, and lead author of the study, said in a news release. “Extensive studies performed in a variety of cancer models have shown that S63845 potently targets cancer cells dependent on MCL1 for their survival.”
S63845 targets cancer cells by activating the BAX/BAK-dependent mitochondrial apoptotic pathway. In vivo, S63845 shows potent anti-tumor activity with an acceptable safety margin as a single agent in several cancers. The authors also noted that, MCL1 inhibition, either alone or in combination with other anti-cancer drugs, proved effective against several solid cancer-derived cell lines. “These results point towards MCL1 as a target for the treatment of a wide range of tumors,” they concluded.
Sources: Kotschy A, Szlavik Z, Murray J, et al. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Nature. 2016;538:477-82; Walter and Eliza Hall Institute press release, October 20, 2016.