Bazedoxifene

Bazedoxifene (CAS No. 198481-32-2) is a third-generation selective estrogen receptor modulator (SERM), primarily used for the prevention and treatment of postmenopausal osteoporosis caused by decreased endogenous estrogen levels. It can effectively reduce the risk of vertebral and non-vertebral fractures without stimulating the human breast. As a specific ligand for estrogen receptors (ERs), it features an indole-based core binding domain and can competitively inhibit the binding of 17β-estradiol to ERα and ERβ [1-3], with IC₅₀ values of 23~26 nM for ERα and 85~99 nM for ERβ [1,3]. It exhibits tissue selectivity in physiological effects: acting as an agonist in the bone, cardiovascular system, and central nervous system (CNS), while functioning as an antagonist in the mammary gland and endometrium. Cell experiments show that Bazedoxifene has no intrinsic ER agonist activity in MCF7 cells and does not affect cell proliferation, but it can significantly inhibit 17β-estradiol-induced transcriptional activation and cell proliferation [3]. In animal studies, ovariectomized rats administered Bazedoxifene at a daily dose of 0.3 mg/kg or 3.0 mg/kg for 6 consecutive weeks exhibited bone-protective effects, effectively preventing bone loss, increasing bone mineral density, and significantly improving the compressive strength of the fifth lumbar vertebra. Among these doses, the 3.0 mg/kg daily dose exerted a moderate stimulatory effect on the rat uterus, only causing a slight increase in uterine wet weight, and the drug showed no ER agonist effect on rat vasomotor activity [2,3].

References:

[1] de Villiers TJ.  Bazedoxifene: a novel selective estrogen receptor modulator for postmenopausal osteoporosis. Climacteric. 2010 Jun;13(3):210-8.

[2] Duggan ST, McKeage K.  Bazedoxifene: a review of its use in the treatment of postmenopausal osteoporosis. Drugs. 2011 Nov 12;71(16):2193-212.

[3] Kawate H, Takayanagi R.  Efficacy and safety of bazedoxifene for postmenopausal osteoporosis. Clin Interv Aging. 2011;6:151-60.