Bazedoxifene

Bazedoxifene is a third generation SERM that displays estrogenic effects in bone and the cardiovascular system, but functions as an antiestrogen in the breast and uterus. 

Raloxifene is an estrogen agonist on bone but an antagonist on the breast and uterus. It is approved for prevention and treatment of postmenopausal osteoporosis. Other estrogen agonists/antagonists maybe approved soon (e.g., bazedoxifene, lasofoxifene). 

Indoles Bazedoxifene (WAY-140424)1 Pipendoxifene (ERA-923)1 Wyeth Wyeth/Ligand... 

In addition to lasofoxifene and arzoxifene, bazedoxifene (TSE-424, WAY-140424) is one of the newer SERMs in advanced Phase III clinical development for the prevention and treatment of postmenopausal osteoporosis. In pre-... 

Lasofoxifene is a SERM that also protects from bone loss, reduces cholesterol levels, and exerts a positive effect on bone strength in rats, specifically in male models (Ma et al. 2002). This compound is in the final stages of clinical development. Two other SERMs also in advanced phase III trials are bazedoxifene and arzoxifene, both with protective effects against ovariectomy-induced bone loss. Arzoxifene has shown both bone remodeling reduction with positive effects on bone quality as well as a reduction in cholesterol levels in oophorectomized rats (Biskobing2003). 

In advanced (phase III) stages of their clinical development, three SERMs are currently on the horizon bazedoxifene, lasofoxifene, and arzoxifene. What these new molecules can offer will be known shortly in a field - the selective regulation of hormone receptor - that has opened unsuspected perspectives for the better management of patients. 

Bazedoxifene has also demonstrated in experimental studies its ability to inhibit the growth of ER(+) tumors in mice and rats in the absence of uterotrophic effects (Greenberger et al. 2001). At the present time bazedoxifene s ability to counteract the estrogenic effects of CEE at the levels of both breast and endometrium is being tested in a multicentric study comparing calcium + vitamin D to bazedoxifene with and without a low dose of CEE in mild symptomatic postmenopausal women. 

Bazedoxifene acetate is a third-generation SERM. In in vitro studies bazedoxifene competitively inhibited 17y0-estradiol binding to both ERa (Ki = 0.1 nM) and ER/3 (Ki = 0.03 nM). Bazedoxifene s ability to competitively bind to ERs... 

Bazedoxifene s primary indication is the treatment and prevention of postmenopausal osteoporosis (Miller et al. 2002). In animal models bazedoxifene displays estrogenhke agonistic activity on bone loss and significantly reduces total cholesterol levels with doses as low as 0.1 mg/kg (Miller et al. 2002). Also in these models, there is no evidence of an estrogenic stimulatory effect on the endometrial epithelial cell (Miller et al. 2001). 

Clinical phase I and II data reveal bazedoxifene to be safe, very well tolerated, and efficacious. Phase III trials are currently in progress. 

The novel SERMs, which include bazedoxifene and ospemifene (also known as deaminohydroxy-toremifene), are being investigated for the prevention and treatment of osteoporosis in post-menopausal women in phase III clinical trials [151,165]. The non-steroidal SERM lasofoxifene (CP-336156) [151], currently under consideration by the Food and Drug Administration for both prevention of osteoporosis and urogenital atrophy, may have potential for... 

Bazedoxifene (10) Viviant Conbriza Mixed Agonist/ Antagonist Osteoporosis Wyeth/Ligand Approved 2009 (EU)... 

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