STAPLED, MUTANT 3 CELL PENETRATING PEPTIDE FOR BCR-ABL INHIBITION

Each year, over 8,000 cases of chronic myeloid leukemia (CML) are diagnosed in the United States. Current first-line treatment utilizes tyrosine kinase inhibitors (TKIs) that demonstrate high potency against CML. This treatment is limited, however, by mutations in Bcr-Abl (a gene fusion found in the majority of patients with CML) that confer resistance.
A novel, stapled, mutant three-cell penetrating peptide for Bcr-Abl inhibition prevents the oncogenic function of Bcr-Abl without triggering resistance-causing mutations. The peptide inhibitor consists of a modified Bcr coil that preferentially interacts with Bcr-Abl and prevents dimerization. The coil has a leukemia specific cell penetrating petptide and a hydrocarbon staple to ensure the peptide will only bind to and inhibit Bcr-Abl cancer cells. This causes cancer cell death while leaving non-cancer cells healthy and unaffected. The smaller peptide is also easier to deliver and demonstrates increased cell permeability.