Stapled Cell Penetrating Peptide Inhibitor Of Bcr‐abl

Peptide inhibitor of Bcr-Abl chimeric protein that provides cell-specific targeting for apoptosis of cancer cells in chronic myeloid leukemia.

Each year over 8,000 cases of chronic myeloid leukemia (CML) are diagnosed in the United States. Current 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 peptide 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.

Optimization & Testing

• Improves stability, cell selectivity, and specificity.
• Demonstrates better proteolytic resistance.
• Increases half-life and serum stability.
• Reduces toxicity to normal cells.

Bruno, B.J., Lim, C.S. (2015). Inhibition of Bcr-Abl in human leukemic cells with a coiled-coil protein delivered by a leukemia-specific cell-penetrating peptide. Molecular Pharmaceutics. 12(5):1412-21 doi: 10.1021/mp500701u

Publication Number: US-2017-0174750-A1
Patent Title: Peptide Inhibitors of BCR-ABL Oligomerization
Jurisdiction/Country: United States
Application Type: Non-Provisional

Jason Young
(801) 587-0519
jason.r.young@utah.edu