Prodrugs and Conjugates of Thiol- and Selenol-Containing Compounds to Treat Cancer and Radiation Exposure
Providing selenium in a nontoxic form is a distinct challenge. Organic forms appear to be superior to inorganic ones. This technology discloses a method for the design, synthesis and evaluation of prodrugs of selenocysteine. The prodrugs of selenocysteine may find wide utility in protection/prevention strategies, such as chemoprotection and anti-radiation, by providing selenium, which is a critical component of an enzyme involved in the body�s natural defensive mechanisms.
The market applications are multiple and varied:
*The prodrugs of cysteine feed into the biosynthesis of the endogenous protector, glutathione. Glutathione with antioxidative properties protects the body against whole hosts of toxic agents and situations.
*Chemoprotection against drug (acetaminophen) overdose, solvent exposure, radiation, radiation or chemotherapy of cancer, cataracts, biological and chemical warfare agents.
*Chemopreventive activity against a tobacco-derived lung carcinogen
*There is evidence that selenium deficiency may contribute to development of a form of heart disease, hypothyroidism and a weakened immune system.
Stage of Development
Patent numbers 6,340,746 and 6,841,536 have been issued by the U.S. Patent and Trademark Office. Other patents related to these technologies are also pending. These technologies are part of an active and ongoing research program and have been validated in animal experiments. They are available for developmental research support and/or licensing under either exclusive or non-exclusive terms.
*El-Sayed WM, Roberts JC, Franklin MR et al. Effect of selenium-containing compounds on hepatic chemoprotective enzymes in mice. Toxicology 2006 Mar 15;220(2-3):179-88.
*Li L, Franklin MR, Roberts JC et al. Chemopreventive activity of selenocysteine prodrugs against tobacco-derived nitrosamine (NNK) induced lung tumors in the A/J mouse. Journal of Biochemical and Molecular Toxicology 2005;19(6):396-405.
*See also: http://www.pharmacy.utah.edu/pharmtox/faculty/franklin.html
Tarek Aboul-Fadl, Pamela Dominick, Jeanette Roberts, Pamela Cassidy, Britta Wilmore, Megan Short, Michael Franklin
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