MATERIALS FOR INHIBITING AROMATASE AND METHOD OF USING THE SAME TO DIAGNOSE, TREAT AND MONITOR BREAST CANCER

摘要

Disclosed herein are triphenylalkenes that can be used to inhibit aromatases. The inhibitory potency order of the tested compounds was as follows: norendoxifen » 4,4'-dihydroxy- tamoxifen > endoxifen > N-desmethyl-tamoxifen, N-desmethyl-4'-hydroxy-tamoxifen, tamoxifen-N-oxide, 4'-hydroxy-tamoxifen, N-desmethyl-droloxifene > 4-hydroxy-tamoxifen, tamoxifen. Norendoxifen inhibited recombinant aromatase via a competitive mechanism with a K i of 35 nM. Norendoxifen inhibited placental aromatase with an IC50 of 90 nM, while it inhibited human liver CYP2C9 and CYP3A with IC50 values of 990 and 908 nM respectively. Inhibition of human liver CYP2C19 by norendoxifen appeared even weaker. No substantial inhibition of CYP2B6 and CYP2D6 by norendoxifen was observed. These compounds, and pharmaceutically acceptable formulations of these compounds, can be used to treat diseases, diagnose and monitory conditions, including some forms of breast cancer. Such compounds can be used alone or in combination with other therapies and therapeutic compounds for treating diseases such as cancer.