Synthetic Steroid Garners Wider Role

Mifepristone, better known as RU-486, is a synthetic steroid that outcompetes the pregnancy steroid hormone progesterone in binding to progesterone receptors. As a result, mifepristone is effective at inducing abortion and as a contraceptive. A research team led by Wolfgang S. L. Strauss of the University of Ulm, in Germany, and Hans-Wolfgang Schramm of the University of Graz, in Austria, now reports the synthesis of mifepristone derivatives that could take advantage of the drug's progesterone-receptor binding to advance diagnostic imaging and cancer treatment (J. Med. Chem., DOI: 10.1021/jm800985z). The researchers replaced one methyl group of the steroid's dimethylaminophenyl substituent with various linker groups to which a fluorescein dye or additional anticancer drug can be attached. These conjugates could be designed to retain or cleave the dye or anticancer drug once mifepristone enters cancer cells. In breast cancer cell assays, the team identified several derivatives for which adding the linker nominally affects mifepristone's bioactivity, a prerequisite to making the strategy practical.