Summary:

The National Cancer Institute (NCI) seeks licensees for the further development of a family of novel iodonium analogs as therapeutics for cancer and/or chronic inflammatory conditions.

Description of Technology:

Diverse human cancers like colorectal, pancreatic, ovarian, melanoma, and pre-cancers express NADPH oxidases (NOX) at high levels. Reactive oxygen species (ROS) produced from metabolic reactions catalyzed by NOX in tumors are essential to the tumor’s growth and play a key role in inflammation-related conditions. Though drugs that inhibit ROS production by NOX could be effective against a variety of human cancers and chronic inflammation-related conditions, these types of drugs are not widely available.

Investigators in NCI’s Developmental Therapeutics Branch have discovered a family of novel analogs of diphenylene iodonium (DPI) and di-thienyl-iodonium (DTI) as inhibitors of NOX and other flavin dehydrogenases for the treatment and prevention of cancer and chronic inflammation-related conditions. Several of these inhibitors displayed in vitro potency that were superior to their parent molecules and were effective in inhibiting cell growth, ROS production, NOX1 mRNA expression, and NOX isoform activity in multiple cancer cell lines, including those representing acute lymphocytic leukemia, chronic myelogenous leukemia, myeloma, large cell immunoblastic lymphoma, non-small cell lung cancer, colon, melanoma, and renal cancer. In vivo validation of parent molecules DPI and DTI using human colon cancer xenografted mice yielded a statistically significant reduction in the average rate of tumor growth in mice administered either DPI or DTI compared to control mice.

The National Cancer Institute (NCI) seeks licensees for the further development of these novel iodonium analogs as therapeutics for cancer and/or chronic inflammatory conditions.

Potential Commercial Applications:

• Anti-cancer therapeutic for tumors that overexpress NOXs or depend on ROS to proliferate, such as colorectal, pancreatic, and ovarian cancers
• Therapeutic for chronic inflammatory conditions, such as diabetes, neuropathies, chronic pancreatitis, and inflammatory bowel disease

Competitive Advantages:

• Increased potency which may facilitate lower dosing concentrations needed
• Optimized specificity and selectivity which may lessen risk of off-target effects
• Potential to be first-in-class drug