Scientists at Beryllium Develop a Robust Platform for Structure-Guided Drug Discovery against MCL1

MCL1 is one of the top-ten most amplified genes in all of human cancer and is vital to tumor development and cancer progression. Although MCL1 is a well-known cancer drug target, obtaining ligand-bound crystal structures has proven to be difficult.   In collaboration with the Broad Institute of MIT and Harvard, Scientists at Beryllium developed a robust crystallographic platform for MCL1 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 MCL1 and opens the door to structure based drug design. 

Clifton et al describe their work in their recent PLOS One publication, where the first Apo and fragment bound x-ray structures of MCL1 are described. These structures provide important breakthroughs for MCL1 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 MCL1 in a non-ligand dependent manner.

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Using our biology-first, target-centric approach and established platforms, we provide research services and engage in collaborations with commercial and academic partners.   Our teams of experienced scientists work closely with our clients to help manage and advance their goals by complementing their capabilities and resources.