Reference #: 00812
Potential Applications:
These Protein Arginine Deiminase Inhibitors aid in the treatment of cancer and arthritis.
Advantages and Benefits:
· The most potent inhibitors of PAD4 activity known to date· Have in vivo applicability· Exhibit cytotoxicity towards cells of cancerous lineage without affecting non-cancerous cells· Trigger cell differentiation into non-cancerous granulocytes
Background:
Cancer is a leading cause of mortality worldwide, killing nearly 8 million people every year and costing close to $125 billion annually. An estimated 1.5 million adults in the U.S. suffer from rheumatoid arthritis. Both diseases negatively affect the quality of life of the patient and burden caretakers. New and improved treatment options are needed that effectively treat these costly diseases.
Invention Description:
This technology identifies two potent, irreversible inactivators targeting Protein Arginine Deiminases (PADs), a family of enzymes that are believed to play roles in various human diseases, including rheumatoid arthritis (RA) and cancer. These second generation haloacetamidine-based PAD inhibitors contain either a fluoro- or a chloro-acetamidine warhead in place of the guanidinium moiety of arginine containing substrates. These inhibitors, which are the most potent known to date, show potential for the treatment of cancer in two ways: i) they exhibit cytotoxicity towards cancer derived cell lines and ii) they cause malignant cells to differentiate into non-cancerous cells. The efficacy of these compounds is even more pronounced when used in combination with the known chemotherapeutic doxorubicin.