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Dr. Anna Marie Skalka and colleagues of Fox Chase Cancer Center have discovered that ATR kinase or one or more of its protein substrates are a target for discovery of anti-retroviral drugs. Inhibition of ATR kinase in human cells interrupts the integration of retroviral DNA into host cells, resulting in cell death.

ATR (ATM and rad3 related) kinase and ATM (ataxia telangiectasia mutated) kinase are human checkpoint kinases. These kinases are known to be involved in radiation sensitivity and are under investigation as targets for cancer therapy.

Caffeine and caffeine-related methylxanthines, such as theophylline, inhibit ATR (ATM and rad3 related) kinase. Theophylline is a widely used asthma medication, and its effects mimic those of caffeine. Studies by Skalka and colleagues indicate that these compounds block viral DNA integration through inhibition of ATR. Therefore, theophylline and/or derivatives may act as effective therapeutic agents in the fight against HIV. The major category of HIV medications includes reverse transcriptase or protease inhibitors, which block viral DNA synthesis and allow HIV to reproduce non-infectious copies of itself, respectively. By inhibiting viral DNA integration, theophylline can block establishment and persistence of infection, thereby decreasing the quantity of HIV created in the body. Hindrance of HIV reproduction by targeting cellular functions can thwart the occurrence of resistant variant strains of HIV that often lead to cross-resistance, as is seen with reverse transcriptase and protease inhibitors.

Applications

• Anti-retroviral drug discovery
• Compound screening
• Basic retroviral research

Opportunity

Licenses are available for research and commercial use for:

• ATR kinase or its protein substrates as target(s) for anti-retroviral drug development
• Cellular assay for screening for anti-retroviral activity via ATR kinase inhibition

Patent Status: A U.S. utility patent application has been filed.

For licensing information, contact

Inna Khartchenko, MS, MBA
Director, Licensing
Associate Director, Office of Corporate Alliances
Fox Chase Cancer Center
610 Old York Road, Room 409
Jenkintown, PA 19046
Tel.: 215-214-3989
Fax: 215-214-1440
inna.khartchenko@fccc.edu