Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity.

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Komm BS, Kharode YP, Bodine PV, Harris HA, Miller CP, Lyttle CR

Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity.

Endocrinology. 2005 Sep;146(9):3999-4008. Epub 2005 Jun 16.

PubMed ID

15961563 [ View in PubMed

]

Abstract

We assessed the preclinical characteristics of a novel, stringently screened selective estrogen receptor modulator, bazedoxifene acetate, including its ability to bind to and activate estrogen receptors and promote increased bone mineral density and bone strength in rats, and the effects impacting the uterine endometrium, breast cancer cell proliferation, and central nervous system-associated vasomotor responses in an animal model. Bazedoxifene bound to estrogen receptor-alpha with an IC50 of 26 nm, an affinity similar to that of raloxifene. Bazedoxifene did not stimulate proliferation of MCF-7 cells but did inhibit 17beta-estradiol-induced proliferation with an IC50 of 0.19 nm. In an immature rat uterine model, bazedoxifene (0.5 and 5.0 mg/kg) was associated with less increase in uterine wet weight than either ethinyl estradiol (10 microg/kg) or raloxifene (0.5 and 5.0 mg/kg). Histological analysis revealed that coadministration of bazedoxifene also appeared to reduce raloxifene-stimulated endometrial luminal epithelial cell and myometrial cell hypertrophy. In ovariectomized rats, bazedoxifene was associated with significant increases in bone mineral density at 6 wk, compared with control, and better compressive strength of bone samples from the L4 vertebrae, compared with samples from ovariectomized animals. In the morphine-addicted rat model of vasomotor activity, bone-sparing doses of bazedoxifene alone were not associated with 17beta-estradiol inhibition of increased vasomotor activity. Bazedoxifene acetate represents a promising new treatment for osteoporosis, with a potential for less uterine and vasomotor effects than selective estrogen receptor modulators currently used in clinical practice. Controlled clinical trial data will be needed to confirm these effects.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Bazedoxifene	Estrogen receptor beta	Protein	Humans	Unknown	Not Available	Details

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Bazedoxifene	Approved Investigational	LIPC	3990	upregulated	bazedoxifene results in increased expression of LIPC mRNA	15q21.3
Estradiol	Approved Investigational Vet Approved	LIPC	3990	upregulated	Estradiol results in increased expression of LIPC mRNA	15q21.3