ACOLBIFENE

Description

The prodrug EM-800 is an orally active nonsteroidal anties trogen and is a triphenylethylene rigid analogue. EM-800 undergoes ester hydrolysis to the active m etabolite acolbifene. This fourth-generation antiestrogen is 200-fold more potent than tam oxifen in breast and uterine cancer cells and is effective in patients for whom tamoxifen therapy has failed. The mechanistic rationale for the effectiveness of acolbifene in tamoxifen-resistant tumors is based on the fact that it inhibits both the AF-1 and AF-2 activation pathways and does not poss ess any intrinsic estrogenic action. Acolbifene enjoys a 60% breast cancer cure rate. Structurally, acolbifene resembles raloxifene, with a benzopyran ring substituted for the benz othiophene ring. An additional benefit observed with acolbifene is its protective effect on bone loss. Adverse effects include nausea and vomiting.