A newly discovered compound - S63845 - targets a protein of the BCL2
family, called MCL1, which is essential for the sustained survival of
The compound has been discovered jointly by international pharmaceutical
company Servier, headquartered in France, and Vernalis (R&D), a
company based in the UK.
‘The Servier compound presents a new way to efficiently kill cancerous cells and holds promise for the treatment of several types of cancer.’
The research presents a new way to efficiently kill these cancerous
cells and holds promise for the treatment of blood cancers such as acute
myeloid leukemia, lymphoma and multiple myeloma, as well as solid
cancers such as melanoma and cancers of the lung and breast. It is
published online today in the journal Nature
Institute scientist Associate Professor Guillaume Lessene, who led
the Walter and Eliza Hall Institute's research team in Melbourne,
Australia, said the work provided the first clear preclinical evidence
that inhibiting MCL1 was effective in targeting several cancer types.
"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,"
Associate Professor Lessene said. "Extensive studies performed in a
variety of cancer models have shown that S63845 potently targets cancer
cells dependent on MCL1 for their survival."
The institute team of Associate Professor Lessene worked with
haematologist Associate Professor Andrew Wei and Dr Donia Moujalled from
The Alfred Hospital and Servier scientists, to demonstrate that not
only was S63845 effective against several cancer types, but that it
could also be delivered at doses that were well tolerated by normal
Dr. Olivier Geneste, Director of Oncology Research at Servier, said
this preclinical research represented major findings regarding the
druggability of MCL1, a valuable and highly challenging target. "S63845
was discovered through collaboration with the fragment and structure
based discovery expertise at Vernalis," he said. "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."
Associate Professor Lessene said the research provided further
evidence of the usefulness of a new class of anti-cancer drugs called
BH3 mimetics. "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."