This invention offers a novel approach to the prevention of lung cancer via the selective inhibition of the enzyme in the human lung that activates tobacco compounds into carcinogens.
Lung cancer is one of the leading causes of cancer-related deaths in men and women worldwide. Long term smoking and exposure to smoke are critical factors in lung cancer causation. Current preventative methods attempt to alter smoker behavior, replace nicotine delivery, or act at nicotine receptors to reduce the physiological effects that make smoking addictive. These preventative methods have varying success and, as such, an innovative approach to preventing lung cancer would have valuable industry applications.
-Reduce risk of lung cancer in smokers.
-Reduce risk of lung cancer in those exposed to second-hand smoke.
Cytochrome P450 2A13 is an enzyme in the human lung that activates a procarcinogenic compound found in tobacco (NNK) into carcinogens. NNK is either cleared from the body as the N-oxide or activated by cytochrome P450 2A13 (CYP2A13) in human lung tissues to form two different carcinogens that then alkylate DNA. Selectively inhibiting cytochrome P450 2A13 could prevent in vivo generation of the NNK metabolites that cause lung carcinoma in smokers. Research has shown that people with a naturally-occurring inactive version of CYP2A13 are physiologically normal and, if smokers, appear to get lung cancer at lower rates than individuals with a wild type version of CYP2A13.
-Chemopreventative agents provide physicians a novel approach to work with smokers to reduce their disease risk.
-Candidate inhibitors are selective for CYP2A13 in the lung over CYP2A6 in the liver.
-Lead compounds show low genetic and cardiac toxic