Newly-discovered compound blocks an essential protein in sustaining tumor growth.
A newly-discovered compound was found to block the protein MCL1, which is essential for the sustained growth of up to one-quarter of all cancer types.
This finding points to the potential development of new treatment options for blood cancers, as well as solid cancers such as of the lung and breast. The researchers demonstrated the efficacy of the compound S63845 against some cancer types and the potential for it to be delivered in doses that are well tolerated by normal cells in a 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,” said lead researcher Guillaume Lessene. “Extensive studies performed in a variety of cancer model shave shown that S63845 potently targets cancer cells dependent on MCL1 for their survival.”
MCL1 is a challenging and valuable target for cancer, and the preclinical research indicated major findings on the druggability of this protein.
“S63845 was discovered through collaboration with the fragment and structure based discovery expertise at Vernalis,” said researcher Olivier Geneste. “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.”
Researchers added that the study’s findings provided additional evidence on the usefulness of BH3 mimetics, a new class of anti-cancer drugs.
“BH3 mimetics inhibit a group of proteins known as the ‘pro-survival BCL-2 proteins’,” Lessene 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 4 years ago.”