@entity172 are represented by a diverse group of compounds. Within this large family of molecules are tissue-selective estrogens that have been classified as selective @entity172 receptor modulators (SERMs). These compounds are characterized by the fact that they exhibit both @entity172 agonist and antagonist activity dependent upon the gene promoter and target tissue being examined. SERMs have been intensively studied over the past decade, especially since one, @entity441 , has been approved for the prevention and treatment of @entity170 . While not a replacement for hormone replacement therapy (HRT), @entity441 can be an alternative to it and other treatments for @entity170 . The ideal SERM would provide the positive benefits associated with HRT without the uterine and breast stimulation. @entity441 does achieve some of the benefits of HRT, specifically on the skeleton and lipid metabolism with no apparent uterine effects, and a potential decreased risk of developing @entity0 associated with @entity441 therapy. However, there are a number of parameters that can be improved. A number of SERMs have been evaluated only to fail in development due to, for the most part, uterine safety issues. In order to develop an improved SERM, a stringent screening process was designed to select compounds that did not stimulate the uterus or breast. At the same time, these new compounds would have a positive impact on the skeleton and lipid metabolism with the additional improvement (over @entity441 ) of a neutral effect on hot flashes. Under these strict conditions, @entity178 was developed and, to date, the preclinical pharmacology data have accurately predicted the clinical response demonstrated in phase I and II trials.

Developing a SERM: stringent preclinical selection criteria leading to an acceptable candidate ( XXXX ) for clinical evaluation.

@entity172 :: ('MESH:D004967', 'Chemical') :: ['estrogen', 'Estrogens'] @entity178 :: ('MESH:C447119', 'Chemical') :: ['WAY-140424'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer'] @entity170 :: ('MESH:D010024', 'Disease') :: ['postmenopausal osteoporosis', 'osteoporosis'] @entity441 :: ('MESH:D020849', 'Chemical') :: ['raloxifene', 'Raloxifene']
@entity178 :: (MESH:C447119,Chemical) :: ['WAY-140424']
