Journal of Biological Chemistry Publication

| 10 October 2025

Congratulations to Ivan Shapovalov for his recent publication in the Journal of Biological Chemistry which describes a combination of elegant in vitro biochemical structure-function studies and in silico modeling to explore the potential of inhibiting the Calpain-1 and Calpain-2 proteases by disrupting interactions between their catalytic and regulatory subunits.

This study included a collaboration with Dr. Emil Alexov from Clemson University in South Carolina and two of his PhD students who performed virtual in silico screens of large chemical libraries to identify small molecules with the potential to bind at the interfaces of the Calpain catalytic and regulatory subunits and thereby inhibit these proteases. Ivan and Victoria Lewtas then used biochemical approaches to measure the affinities of the Calpain subunit interactions and test the ability of selected hits from the virtual screen to block those interactions and inhibit protease activity.

This work forms the foundation of ongoing studies to develop allosteric inhibitors of Calpain that can be tested in pre-clinical models of cancer. They hope this will translate to clinically effective calpain inhibitors that can suppress the metastatic behaviour of cancer cells and improve the survival of patients with aggressive cancers.

This work was supported by a grant from the CIHR. Read their published work here: Quantification and structure–function analysis of calpain-1 and calpain-2 protease subunit interactions - PMC

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