Researchers have identified a new compound called S63845 that blocks the growth of several different types of cancer, including lymphoma, according to a study published in the journal Nature.
The study, “The MCL1 Inhibitor S63845 Is Tolerable And Effective In Diverse Cancer Models,” was conducted by researchers from the Walter and Eliza Hall Institute and the pharmaceutical company Servier.
It showed that the compound S63845 targets the pro-survival protein MCL1, killing cancer cells dependent on this protein to survive. Such cancers include lymphoma, acute myeloid leukemia, multiple myeloma, melanoma, and lung and breast cancers.
“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, 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.”
Researchers also observed that S63845 was effective when delivered at doses that were well tolerated by normal cells.
The MCL-1 protein belongs to a family of cell death proteins — the BCL-2 family — which can be targeted by a group of anti-cancer compounds called the BH3 mimetics. According to Lessene, the results obtained with S63845 further support the usefulness of these drugs.
“BH3 mimetics inhibit a group of proteins known as the ‘pro-survival BCL-2 proteins,'” he said. “MCL1 is a member of this protein family, and inhibiting it activates the process of programmed cell death. Walter and Eliza Hall Institute researchers revealed the role of BCL-2 in cancer more than 28 years ago and the essential role of MCL1 for the survival of malignant cells four years ago.”
The promising results obtained in the study point toward MCL1 as a valuable target for the treatment of a wide range of tumors.
“S63845 was discovered through collaboration with the fragment and structure based discovery expertise at Vernalis,” said Olivier Geneste, director of oncology research at Servier. “As part of the ongoing Servier/Novartis collaboration on this target class, clinical development of a MCL1 inhibitor should be launched in the near future.”