Rationally Designed Aromatase Inhibitors as Anti-Breast Cancer Agents
have developed exemestane-based vinyl diazo compounds that act as aromatase
inhibitors to be used in the treatment of cancer, particularly breast and
ovarian cancer. Exemestane is structurally related to androstenedione and acts
as an irreversible, steroidal aromatase inactivator. Our aromatase inhibitors
are based upon the steroid scaffold and contain inserted alcohols and acids.
Biological assessments of our compounds show improved inhibition, particularly
those containing an alkyne derived side-chain.
is over-expressed in >75% of breast cancer lines. The triazoles Letrozole and
Anastrozole are used as current medications; however, current aromatase
inhibitors are not specific with their target activity. This non-specific
binding can increase the risk of bone disease. In addition, many patients that
are chronically treated with tamoxifen and/or other aromatase inhibitors develop
acquired resistance to these drugs. Our novel compounds would provide potential
alternatives for treatment that are also specific with their target
Stage & Potential Market
testing is underway to investigate the stereoselectivity of the insertion
prolonged treatments, acquired resistance to current aromatase inhibitors that
are on the market is expected to occur in a majority of breast cancer
of aromatase inhibitors with specific activity may decrease potentially
debilitating side effects including bone loss.
aromatase in a potent and specific manner.
alternatives to the current medications that act as non-specific aromatase