The present application is based on the remarkable finding that non-calorigenic thyroid hormones mediate tumor cell apoptosis. A selected lead compound has been identified and shown to interact with microtubules. This compound, DIME, is non-toxic at 1-2 gm/kg/day yet demonstrates potent anti-cancer synergism with the vinca alkaloids. Patents (US #'s 6,017,958; 5,922,775; 5,736,576) have been issued covering the use of DIME and related compounds. This grant seeks support to carry out preclinical studies to support filing an IND for human clinical trials. Specifically, in Phase I we will synthesize DIME in order to carry out expanded in vitro cytotoxicity studies and anti-human tumor xenograft testing in mice. The goal of Phase II studies is to file an IND after expanded preclinical functional models, toxicology and GMP production are completed.
The market for a novel non-toxic agent for cancer is substantial.
