MCL-1 is one of the top-ten most amplified genes in all of human cancer and is vital to tumor development and cancer progression. In collaboration with the Broad Institute of MIT and Harvard, scientists at Beryllium developed a robust crystallographic platform for MCL-1 that uses a combination of fusion protein and sequence engineering.
Unlike previously available structures based on ligand dependent interactions, the new methods allow for systematic screening against MCL-1 and opens the door to structure based drug design.
Clifton et al describe their work in a recent PLOS One publication, where the first Apo and fragment bound x-ray structures of MCL-1 are described.
These structures provide important breakthroughs for MCL-1 drug discovery by providing insight into conformational changes that occur upon ligand binding. In addition, the approach allows for the observation of ligand binding to MCL-1 in a non-ligand dependent manner.
"This is an important development in the enablement of a fragment and structure-based drug design platform for MCL-1," said Dalia Cohen, Ph.D., CSO and Head of Research for Beryllium.
"With this platform, we are now uniquely suited to screen and explore structure activity relationships to optimize hits and leads in target development."