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Details

Stereochemistry ACHIRAL
Molecular Formula C30H34N2O3
Molecular Weight 470.6026
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BAZEDOXIFENE

SMILES

CC1=C(N(CC2=CC=C(OCCN3CCCCCC3)C=C2)C4=C1C=C(O)C=C4)C5=CC=C(O)C=C5

InChI

InChIKey=UCJGJABZCDBEDK-UHFFFAOYSA-N
InChI=1S/C30H34N2O3/c1-22-28-20-26(34)12-15-29(28)32(30(22)24-8-10-25(33)11-9-24)21-23-6-13-27(14-7-23)35-19-18-31-16-4-2-3-5-17-31/h6-15,20,33-34H,2-5,16-19,21H2,1H3

HIDE SMILES / InChI

Description

Bazedoxifene acetate (WAY-140424; TSE-424) is an oral, nonsteroidal, indole-based selective estrogen-receptor modulator developed by Ligand Pharmaceuticals in collaboration with Wyeth Pharmaceuticals (NJ, USA) (now Pfizer) . It was developed using raloxifene as a template with the benzothiophene core substituted by an indole ring in order to obtain favorable effects on the skeleton and lipid metabolism with the additional improvement of a neutral effect on hot flushes and without stimulating the uterus or the breast. The drug is approved as a monotherapy for the prevention and treatment of osteoporosis and in combination with conjugated estrogens for the treatment of menopausal symptoms and prevention of osteoporosis. Bazedoxifene binds to both ERalpha and ERbeta with high affinity. Bazedoxifene acts as both a receptor agonist and/or antagonist, depending upon the cell and tissue type and target genes. Bazedoxifene decreases bone resorption and reduces biochemical markers of bone turnover to the premenopausal range. These effects on bone remodeling lead to an increase in bone mineral density (BMD), which in turn contributes to a reduction in the risk of fractures. Bazedoxifene functions primarily as an estrogen-receptor antagonist in uterine and breast tissues.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
0.6 nM [IC50]
3.8 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
DUAVEE
Preventing
DUAVEE

Cmax

ValueDoseCo-administeredAnalytePopulation
6.9 ng/mL
20 mg 1 times / day steady-state, oral
BAZEDOXIFENE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
71 ng × h/mL
20 mg 1 times / day steady-state, oral
BAZEDOXIFENE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
30 h
20 mg 1 times / day steady-state, oral
BAZEDOXIFENE plasma
Homo sapiens

Doses

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
The recommended dosage is one tablet (containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg) daily.
Route of Administration: Oral
In Vitro Use Guide
The inhibitory effects of BZA (Bazedoxifene acetate) on MCF-7, T47D, MCF-7:5C, and MCF-7:2A cells were determined. MCF-7 and T47D cells were grown in fully estrogenized media, and MCF-7:5C and MCF-7:2A cells were grown in estrogen-free media and then treated with 10^(−12) to 10^(−6) M BZA for 7 days, and cellular DNA was measured as an index of growth.