Bazedoxifene acetate. Selective estrogen receptor modulator - Treatment and prevention of osteoporosis

In order to develop a new tissue selective estrogen with superior preclinical pharmacology, a multifaceted approach to screening/characterization was employed utilizing a series of in vitro and in vivo models. In vitro transcription data demonstrate that all SERMs are not equivalent. This was especially evident when assessing hepatic lipase promoter activation where bazedoxifene was a relatively potent agonist and raloxifene was inactive. When bazedoxifene and raloxifene uterine responses are compared they are different enough that when codosed, bazedoxifene inhibits the stimulation of the, rodent uterus attributable to raloxifene. There are several preclinical endpoints where the two drugs differ, some subtler than others. The structural differences between bazedoxifene and raloxifene are apparently sufficient to confer differences in their pharmacology, which also supports the potential for development of more refined molecules that could achieve the optimal therapeutic target profile for a SERM. Bazedoxifene acetate's preclinical profile suggests that it is closer to this profile than other currently disclosed SERMs and is "best in class" to date.